Targeted antimicrobial moieties

ABSTRACT

This invention provides novel targeted antimicrobial compositions. In various embodiments chimeric moieties are provided comprising an antimicrobial peptide attached to a peptide targeting moiety that binds a bacterial strain or species.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims benefit of and priority to U.S. Ser. No.61/142,830, filed Jan. 6, 2009, U.S. Ser. No. 61/151,445, filed Feb. 10,2009, U.S. Ser. No. 61/243,905, filed Sep. 18, 2009, and U.S. Ser. No.61/243,930, filed Sep. 18, 2009, all of which are incorporated herein byreference in their entirety for all purposes.

STATEMENT OF GOVERNMENTAL SUPPORT

[Not Applicable]

FIELD OF THE INVENTION

The present invention relates to novel targeting peptides, novelantimicrobial peptides, chimeric moieties comprising novel targetingand/or novel antimicrobial peptides and uses thereof.

BACKGROUND OF THE INVENTION

Antibiotic research at the industrial level was originally focused onthe identification of refined variants of already existing drugs. Thisresulted example, in the development of antibiotics such as newerpenicillins, cephalosporins, macrolides, and fluoroquinolones.

However, resistance to old and newer antibiotics among bacterialpathogens is evolving rapidly, as exemplified by extended beta-lactamase(ESBL) and quinolone resistant gram-negatives, multi-resistantgonococci, methicillin resistant Staphylococcus aureus (MRSA),vancomycin resistant enterococci (VRE), penicillin non-susceptiblepneumococci (PNSP) and macrolide resistant pneumococci and streptococci(see, e.g., Panlilo et al. (1992) Infect Control Hosp Epidemio., 13:582-586; Morris et al. (1995) Ann Intern Me., d 123: 250-259, and thelike). An overuse, or improper use, of antibiotics is believed to be ofgreat importance for triggering and spread of drug resistant bacteria.Microbes have, in many cases, adapted and are resistant to antibioticsdue to constant exposure and improper use of the drugs.

Drug resistant pathogens represent a major economic burden forhealth-care systems. For example, postoperative and other nosocomialinfections will prolong the need for hospital care and increaseantibiotic drug expenses. It is estimated that the annual cost oftreating drug resistant infections in the United States is approximately$5 billion.

SUMMARY OF THE INVENTION

In certain embodiments, novel targeting moieties (e.g., peptides) thatspecifically/preferentially bind to microorganisms (e.g., certainbacteria, yeasts, fungi, molds, viruses, algae, protozoa, and the like)are provided. The targeting moieties can be attached to effectors (e.g.,detectable labels, drugs, antimicrobial peptides, etc.) to form chimericconstructs for specifically/preferentially delivering the effector toand/or into the target organism. In certain embodiments novelantimicrobial peptides that can be used to inhibit (e.g., kill and/orinhibit growth and/or proliferation) of certain microorganisms (e.g.,certain bacteria, yeasts, fungi, molds, viruses, algae, protozoa, andthe like) are provided.

Accordingly, in certain embodiments, a chimeric construct (chimericmoiety) is provided comprising: an effector attached to a peptidetargeting moiety comprising an amino acid sequence found in Table 3and/or Table 12; and/or an antimicrobial peptide comprising an aminoacid sequence found in Table 4 and/or Table 5 attached to a targetingmoiety. In certain embodiments the targeting moiety is a peptidecomprising an amino acid sequence of a peptide found one or more ofTable 3 and Table 12. In certain embodiments the targeting moiety is apeptide comprising two or more amino acid sequences of a peptide foundone or more of Table 3 and Table 12. In certain embodiments thetargeting moiety is a peptide whose amino acid sequence consists of theamino acid sequence of a peptide found in Table 3.

In various embodiments the effector comprises a moiety selected from thegroup consisting of an antimicrobial peptide, an antibiotic, a ligand, alipid or liposome, a agent that physically disrupts the extracellularmatrix within a community of microorganisms, and a polymeric particle.In certain embodiments the effector comprises an antimicrobial peptidecomprising an amino acid sequence found in one or more of Tables 4, 5,14, and Table 15. In certain embodiments the effector comprises anantimicrobial peptide comprising an amino acid sequence found in one ormore of Tables 4, and 5. In certain embodiments the effector comprisesan antimicrobial peptide comprising an amino acid sequence characterizedby a motif selected from the group consisting of KIF, FIK, KIH, HIK, andKIV (e.g., as identified in Table 7). In certain embodiments theconstruct comprises a targeting peptide comprising an amino acidsequence found in Table 3 attached to an antimicrobial peptidecomprising an amino acid sequence found in Table 4 and/or Table 5. Incertain embodiments the construct comprises an antimicrobial peptidecomprising an amino acid sequence found in Table 4 attached to atargeting moiety comprising an amino acid sequence found in Table 3and/or Table 10, and/or Table 12. In certain embodiments the constructcomprises a targeting peptide comprising an amino acid sequence found inTable 3 attached to an antimicrobial peptide comprising an amino acidsequence found in Table 4.

In various embodiments the targeting moiety is chemically conjugated tothe effector (directly or via a linker). In certain embodiments theliker comprises a polyethylene glycol (PEG). In certain embodiments thetargeting moiety is chemically conjugated to the effector via anon-peptide linker found in Table 16. In certain embodiments thetargeting moiety is linked to the effector via a peptide linkage. Incertain embodiments the effector comprises an antimicrobial peptide andthe construct is a fusion protein. In certain embodiments the targetingmoiety is attached to the effector by a peptide linker comprising orconsisting of an amino acid sequence found in Table 16. In certainembodiments any of the constructs and/or peptides described herein bearsone or more protecting groups. In certain embodiments the one or moreprotecting groups are independently selected from the group consistingof acetyl, amide, 3 to 20 carbon alkyl groups, fmoc, tBoc,9-fluoreneacetyl group, 1-fluorenecarboxylic group, 9-florenecarboxylicgroup, 9-fluorenone-1-carboxylic group, benzyloxycarbonyl, xanthyl(Xan), trityl (Trt), 4-methyltrityl (Mtt), 4-methoxytrityl (Mmt),4-methoxy-2,3,6-trimethyl-benzenesulphonyl (Mtr), mesitylene-2-sulphonyl(Mts), 4,4-dimethoxybenzhydryl (Mbh), tosyl (Tos), 2,2,5,7,8-pentamethylchroman-6-sulphonyl (Pmc), 4-methylbenzyl (MeBzl), 4-methoxybenzyl(MeOBzl), benzyloxy (BzlO), benzyl (Bzl), benzoyl (Bz),3-nitro-2-pyridinesulphenyl (Npys),1-(4,4-dimentyl-2,6-diaxocyclohexylidene)ethyl (Dde), 2,6-dichlorobenzyl(2,6-DiCl—Bzl), 2-chlorobenzyloxycarbonyl (2-Cl—Z),2-bromobenzyloxycarbonyl (2-Br—Z), benzyloxymethyl (Bom),t-butoxycarbonyl (Boc), cyclohexyloxy (cHxO), t-butoxymethyl (Bum),t-butoxy (tBuO), t-Butyl (tBu), and trifluoroacetyl (TFA). In certainembodiments the peptide and/or construct comprises a protecting group ata carboxyl and/or amino terminus. In certain embodiments the carboxylterminus is amidated and/or the amino terminus is acetylated. In variousembodiments the chimeric construct and/or peptide is functionalized witha polymer (e.g., comprises polyethylene glycol, cellulose, modifiedcellulose, dextrin, etc.) to increase serum halflife.

In certain embodiments pharmaceutical compositions are provided. Invarious embodiments the pharmaceutical compositions comprise a chimericconstruct as described herein (e.g., a chimeric construct according toany of claims 1-26) and/or an antimicrobial peptide as described herein,in a pharmaceutically acceptable carrier. In certain embodiments thecomposition is formulated as a unit dosage formulation. In certainembodiments the composition is formulated for administration by amodality selected from the group consisting of intraperitonealadministration, topical administration, oral administration, inhalationadministration, transdermal administration, subdermal depotadministration, systemic IV application, ocular administration, andrectal administration.

In certain embodiments isolated antimicrobial peptides are provided. Invarious embodiments the peptides comprise one or more sequences selectedfrom the amino acid sequences listed in Table 4 and/or Table 5 (and/orthe retro, inverso, retroinverso, or beta forms). In various embodimentsthe antimicrobial peptide bears one or more protecting groups e.g., asdescribed herein.

In certain embodiments a composition effective to kill or to inhibit thegrowth and/or of a microorganism and/or the formation and/or maintenanceof a biofilm is provided. The composition typically comprises one ormore isolated antimicrobial peptides, the amino acid sequences of thepeptides comprising one or more sequences selected from the amino acidsequences listed in Table 4 and/or Table 5 (and/or their retro, inverso,or retroinverso forms). In certain embodiments the composition iseffective to kill or inhibit the growth and/or proliferation of a yeastor fungus, and the composition comprises one or more peptides, the aminoacid sequences of the peptides comprising one or more sequences selectedfrom the group of amino acid sequences listed in Table 4 and/or Table 5identified (e.g., in those tables) as effective to effective to kill orinhibit the growth and/or proliferation of a yeast or fungus. In certainembodiments the composition is effective to kill or inhibit the growthand/or proliferation of Aspergillus niger and the composition comprisesone or more peptides, the amino acid sequences of the peptidescomprising one or more sequences selected from the group of amino acidsequences listed in Table 4 and/or Table 5 identified as effective toeffective to kill or inhibit the growth and/or proliferation ofAspergillus niger. In certain embodiments the composition is effectiveto kill or inhibit the growth and/or proliferation of C. albicans andthe composition comprises one or more peptides, the amino acid sequencesof the peptides comprising one or more sequences selected from the groupof amino acid sequences listed in Table 4 and/or Table 5 identified aseffective to effective to kill or inhibit the growth and/orproliferation of C. albicans. In certain embodiments the composition iseffective to kill or inhibit the growth and/or proliferation of T.rubrum and the composition comprises one or more peptides, the aminoacid sequences of the peptides comprising one or more sequences selectedfrom the group of amino acid sequences listed in Table 4 and/or Table 5identified as effective to effective to kill or inhibit the growthand/or proliferation of T. rubrum. In certain embodiments thecomposition is effective to kill or inhibit the growth and/orproliferation of a bacterium, and the composition comprises one or morepeptides, the amino acid sequences of the peptides comprising one ormore sequences selected from the group of amino acid sequences listed inTable 4 and/or Table 5 identified as effective to effective to kill orinhibit the growth and/or proliferation of a bacterium. In certainembodiments the composition is effective to kill or inhibit the growthand/or proliferation of a gram positive bacterium, and the compositioncomprises one or more peptides, the amino acid sequences of the peptidescomprising one or more sequences selected from the group of amino acidsequences listed in Table 4 and/or Table 5 identified as effective toeffective to kill or inhibit the growth and/or proliferation of a grampositive bacterium. In certain embodiments the composition is effectiveto kill or inhibit the growth and/or proliferation of A. naeslundii, andthe composition comprises one or more peptides, the amino acid sequencesof the peptides comprising one or more sequences selected from the groupof amino acid sequences listed in Table 4 and/or Table 5 identified aseffective to effective to kill or inhibit the growth and/orproliferation of A. naeslundii. In certain embodiments the compositionis effective to kill or inhibit the growth and/or proliferation of B.subtilis, and the composition comprises one or more peptides, the aminoacid sequences of the peptides comprising one or more sequences selectedfrom the group of amino acid sequences listed in Table 4 and/or Table 5identified as effective to effective to kill or inhibit the growthand/or proliferation of B. subtilis. In certain embodiments thecomposition is effective to kill or inhibit the growth and/orproliferation of C. difficile, and the composition comprises one or morepeptides, the amino acid sequences of the peptides comprising one ormore sequences selected from the group of amino acid sequences listed inTable 4 and/or Table 5 identified as effective to effective to kill orinhibit the growth and/or proliferation of C. difficile. In certainembodiments the composition is effective to kill or inhibit the growthand/or proliferation of C. jeikeium, and the composition comprises oneor more peptides, the amino acid sequences of the peptides comprisingone or more sequences selected from the group of amino acid sequenceslisted in Table 4 and/or Table 5 identified as effective to effective tokill or inhibit the growth and/or proliferation of C. jeikeium. Incertain embodiments the composition is effective to kill or inhibit thegrowth and/or proliferation of E. faecalis, and the compositioncomprises one or more peptides, the amino acid sequences of the peptidescomprising one or more sequences selected from the group of amino acidsequences listed in Table 4 and/or Table 5 identified as effective toeffective to kill or inhibit the growth and/or proliferation of E.faecalis. In certain embodiments the composition is effective to kill orinhibit the growth and/or proliferation of M. luteus, and thecomposition comprises one or more peptides, the amino acid sequences ofthe peptides comprising one or more sequences selected from the group ofamino acid sequences listed in Table 4 and/or Table 5 identified aseffective to effective to kill or inhibit the growth and/orproliferation of M. luteus. In certain embodiments the composition iseffective to kill or inhibit the growth and/or proliferation of MRSA,and the composition comprises one or more peptides, the amino acidsequences of the peptides comprising one or more sequences selected fromthe group of amino acid sequences listed in Table 4 and/or Table 5identified as effective to effective to kill or inhibit the growthand/or proliferation of MRSA. In certain embodiments composition iseffective to kill or inhibit the growth and/or proliferation of S.epidermidis, and the composition comprises one or more peptides, theamino acid sequences of the peptides comprising one or more sequencesselected from the group of amino acid sequences listed in Table 4 and/orTable 5 identified as effective to effective to kill or inhibit thegrowth and/or proliferation of S. epidermidis. In certain embodimentsthe composition is effective to kill or inhibit the growth and/orproliferation of S. mutans, and the composition comprises one or morepeptides, the amino acid sequences of the peptides comprising one ormore sequences selected from the group of amino acid sequences listed inTable 4 and/or Table 5 identified as effective to effective to kill orinhibit the growth and/or proliferation of S. mutans. In certainembodiments the composition is effective to kill or inhibit the growthand/or proliferation of S. pneumoniae, and the composition comprises oneor more peptides, the amino acid sequences of the peptides comprisingone or more sequences selected from the group of amino acid sequenceslisted in Table 4 and/or Table 5 identified as effective to effective tokill or inhibit the growth and/or proliferation of S. pneumoniae. Incertain embodiments the composition is effective to kill or inhibit thegrowth and/or proliferation of a gram negative bacterium, and thecomposition comprises one or more peptides, the amino acid sequences ofthe peptides comprising one or more sequences selected from the group ofamino acid sequences listed in Table 4 and/or Table 5 identified aseffective to effective to kill or inhibit the growth and/orproliferation of a gram negative bacterium. In certain embodiments thecomposition is effective to kill or inhibit the growth and/orproliferation of A. baumannii, and the composition comprises one or morepeptides, the amino acid sequences of the peptides comprising one ormore sequences selected from the group of amino acid sequences listed inTable 4 and/or Table 5 identified as effective to effective to kill orinhibit the growth and/or proliferation of A. baumannii. In certainembodiments the composition is effective to kill or inhibit the growthand/or proliferation of C. jejuni, and the composition comprises one ormore peptides, the amino acid sequences of the peptides comprising oneor more sequences selected from the group of amino acid sequences listedin Table 4 and/or Table 5 identified as effective to effective to killor inhibit the growth and/or proliferation of C. jejuni. In certainembodiments the composition is effective to kill or inhibit the growthand/or proliferation of E. coli, and the composition comprises one ormore peptides, the amino acid sequences of the peptides comprising oneor more sequences selected from the group of amino acid sequences listedin Table 4 and/or Table 5 identified as effective to effective to killor inhibit the growth and/or proliferation of E. coli. In certainembodiments the composition is effective to kill or inhibit the growthand/or proliferation of F. nucleatum, and the composition comprises oneor more peptides, the amino acid sequences of the peptides comprisingone or more sequences selected from the group of amino acid sequenceslisted in Table 4 and/or Table 5 identified as effective to effective tokill or inhibit the growth and/or proliferation of F. nucleatum. Incertain embodiments the composition is effective to kill or inhibit thegrowth and/or proliferation of E. coli, and the composition comprisesone or more peptides, the amino acid sequences of the peptidescomprising one or more sequences selected from the group of amino acidsequences listed in Table 4 and/or Table 5 identified as effective toeffective to kill or inhibit the growth and/or proliferation of M.xanthus. In certain embodiments the composition is effective to kill orinhibit the growth and/or proliferation of P. aeruginosa, and thecomposition comprises one or more peptides, the amino acid sequences ofthe peptides comprising one or more sequences selected from the group ofamino acid sequences listed in Table 4 and/or Table 5 identified aseffective to effective to kill or inhibit the growth and/orproliferation of P. aeruginosa. In certain embodiments the compositionis effective to kill or inhibit the growth and/or proliferation of P.gingivalis, and the composition comprises one or more peptides, theamino acid sequences of the peptides comprising one or more sequencesselected from the group of amino acid sequences listed in Table 4 and/orTable 5 identified as effective to effective to kill or inhibit thegrowth and/or proliferation of P. gingivalis. In certain embodiments thecomposition is effective to kill or inhibit the growth and/orproliferation of P. mirabilis, and the composition comprises one or morepeptides, the amino acid sequences of the peptides comprising one ormore sequences selected from the group of amino acid sequences listed inTable 4 and/or Table 5 identified as effective to effective to kill orinhibit the growth and/or proliferation of P. mirabilis.

In various embodiments one or more of the peptides comprising thecomposition comprise all “L” amino acids or all “D” amino acids, or amixture of “L” and “D” amino acids. In various embodiments one or moreof the peptides comprising the composition are β peptides. In variousembodiments one or more of the peptides comprising the compositioncomprise one or more protecting groups (e.g. protected carboxyl and/oramino termini). In various embodiments one or more of the peptidescomprising the composition comprise an amide on the carboxyl terminusand/or an acetyl on the amino terminus. In various embodiments thepeptides comprising the composition are in a pharmaceutically acceptablecarrier. In certain embodiments the carrier is suitable foradministration via a route selected from the group consisting of topicaladministration, aerosol administration, administration via inhalation,oral administration, and/or rectal administration.

In various embodiments methods are provided for killing and/orinhibiting the growth and/or proliferation of a microorganism and or fordisrupting and/or inhibiting the growth and/or maintenance of a biofilm,the method comprising contacting the microorganism (or a biofilmcomprising the microorganism) with a chimeric construct as describedherein (e.g., see description above, and/or a chimeric constructaccording to any one of claims 1-29), or with an antimicrobial peptideas described herein, and/or with a composition as described herein(e.g., a composition according to any one of claims 30-65). In certainembodiments the microorganism is a yeast or fungus and the chimericconstruct or composition is a chimeric construct comprising an effectoridentified as killing a yeast or fungus, or a composition comprising anantimicrobial peptide described herein as killing a yeast or fungus. Incertain embodiments the microorganism is a bacterium (e.g., gramnegative and/or gram positive bacterium) and the chimeric construct orcomposition is a chimeric construct comprising an effector identified askilling a bacterium (e.g., gram negative and/or gram positivebacterium), or a composition comprising an antimicrobial peptidedescribed herein as killing a gram negative and/or gram positivebacterium. In certain embodiments the effector is an antimicrobialpeptide. In certain embodiments the microorganism is S. mutans, and thechimeric construct or composition is applied to the oral cavity of ananimal or human, e.g., to reduces the incidence or severity of dentalcaries and/or periodontal disease). In certain embodiments the chimericconstruct or composition preferentially targets Corynebacterium spp. andthe chimeric construct or composition is applied to the skin surface ofan animal or human (e.g., to reduce body odor).

Methods are also provided for disinfecting a surface. The methodstypically involve contacting the surface with one or more chimericconstructs described herein (e.g. a construct according to any one ofclaims 1-29), or a composition as described herein (e.g., a compositionaccording to any one of claims 30-65). In certain embodiments, thesurface comprises a surface of a prosthesis or medical implant. Incertain embodiments the surface comprises a surface of a medical device.In certain embodiments the surface comprises a surface of a plant orfoodstuff. In certain embodiments the chimeric construct and/or theantimicrobial peptide(s) are combined with a second disinfectantselected from the group consisting of other antimicrobial agent is adisinfectant selected from the group consisting of acetic acid,phosphoric acid, citric acid, lactic, formic, propionic acid,hydrochloric acid, sulfuric acid, nitric acid, sodium hydroxide,potassium hydroxide, sodium carbonate, ammonium hydroxide, ethylalcohol, isopropyl alcohol, phenol, formaldehyde, glutaraldehyde,hypochlorites, chlorine dioxide, sodium dichloroisocyanurate,chloramine-T, iodine, povidone-iodine, chlorhexidine, hydrogen peroxide,peracetic acid, and benzalkonium chloride.

In various embodiments the use of a chimeric construct described hereinand/or an antimicrobial composition as described herein (e.g., achimeric construct according to any one of claims 1-29, or a compositionaccording to any one of claims 30-65) in the manufacture of a medicamentfor killing and/or inhibiting the growth and/or proliferation of amicroorganism and/or inhibiting the growth and/or maintenance of abiofilm comprising the microorganism is provided. In certain embodimentsthe microorganism is a yeast or fungus and the chimeric construct orcomposition is a chimeric construct comprising an effector identified askilling a yeast or fungus, or a composition comprising an antimicrobialpeptide described herein as killing a yeast or fungus. In certainembodiments the microorganism is a bacterium (e.g., gram negative and/orgram positive bacterium) and the chimeric construct or composition is achimeric construct comprising an effector identified as killing abacterium (e.g., gram negative and/or gram positive bacterium), or acomposition comprising an antimicrobial peptide described herein askilling a gram negative and/or gram positive bacterium. In certainembodiments the effector is an antimicrobial peptide.

In various embodiments methods are also provided for of detecting abacterium and/or a bacterial film (e.g., a biofilm comprising thebacteria). The methods typically involve contacting the bacterium orbacterial film with a composition comprising a detectable label attachedto a targeting peptide comprising one or more amino acid sequences foundTable 3 and/or Table 12; and detecting the detectable label where thequantity and/or location of the detectable label is an indicator of thepresence of the bacterium and/or bacterial film. In certain embodimentsthe targeting peptide comprises or consists of an amino acid sequence ofa peptide found in Table 3 (and/or the retro, inverso, retroinverso formof the sequence). In certain embodiments the detectable label is a labelselected from the group consisting of a radioactive label, aradio-opaque label, a fluorescent dye, a fluorescent protein, anenzymatic label, a colorimetric label, and a quantum dot.

Certain compositions are also provided comprising a photosensitizing orphotoactivatable agent attached to a targeting peptide (e.g., a peptidecomprising an amino acid sequence of a peptide found in Table 3 and/orTable 12). In certain embodiments the targeting peptide comprises orconsists of an amino acid sequence of a peptide found in Table 3. Incertain embodiments the photosensitizing agent is an agent selected fromthe group consisting of a porphyrinic macrocycle, a porphyrin, achlorine, a crown ether, an acridine, an azine, a phthalocyanine, acyanine, a psoralen, a cucumin, and a perylenequinonoid. In certainembodiments the photosensitizing agent comprises one or more agentsagent shown in any of FIGS. 1-12. In certain embodiments thephotosensitizing agent is attached to the targeting peptide by anon-peptide linker (e.g., a polyethylene glycol (PEG)). In certainembodiments the photosensitizing agent is attached to the targetingpeptide by a non-peptide linker found in Table 16.

In various embodiments methods are provided for killing and/or forinhibiting the growth and/or proliferation of a microorganism or abiofilm comprising a microorganism, where the methods involve contactingthe microorganism or biofilm with a composition comprising aphotosensitizing or photoactivatable agent attached to a targetingpeptide (e.g., a peptide comprising an amino acid sequence of a peptidefound in Table 3 and/or Table 12). In certain embodiments the targetingpeptide comprises or consists of an amino acid sequence of a peptidefound in Table 3. In certain embodiments the photosensitizing agent isan agent selected from the group consisting of a porphyrinic macrocycle,a porphyrin, a chlorine, a crown ether, an acridine, an azine, aphthalocyanine, a cyanine, a psoralen, a cucumin, and aperylenequinonoid. In certain embodiments the photosensitizing agentcomprises one or more agents agent shown in any of FIGS. 1-12. Incertain embodiments the photosensitizing agent is attached to thetargeting peptide by a non-peptide linker (e.g., a polyethylene glycol(PEG)). In certain embodiments the photosensitizing agent is attached tothe targeting peptide by a non-peptide linker found in Table 16. Incertain embodiments the method further comprises exposing themicroorganism or biofilm to a light source. In certain embodiments themicroorganism is a microorganism selected from the group consisting of abacterium (e.g., a gram positive and/or a gram negative bacterium), ayeast, a fungus, a protozoan, and a virus. In certain embodiments thebiofilm comprises a bacterial film. In certain embodiments the biofilmis a biofilm on an implanted or implantable medical device. In certainembodiments the microorganism or biofilm is an organism or biofilm in anoral cavity.

In various embodiments certain formulations are provided. Typicalformulations include, but are not limited to a targeting peptide, anantimicrobial peptide, and/or a STAMP; and a salt at a concentrationcomparable to that found in phosphate buffered saline (PBS) ranging fromabout 0.5×PBS to about 2.5×PBS. In certain embodiments the formulationcomprises a targeting peptide found in Tables 3 or 10. In certainembodiments the formulation comprises an anti-S. mutans peptidetargeting peptide (e.g., as identified in Tables 3 or 12). In certainembodiments the anti-S. mutans targeting peptide has the amino acidsequence TFFRLFNRSFTQALGK (SEQ ID NO:1). In certain embodiments theanti-S. mutans targeting peptide is attached to an antimicrobialpeptide. In certain embodiments the antimicrobial peptide is a peptidefound in Tables 4, 5, or 14. In certain embodiments the antimicrobialpeptide has the amino acid sequence KNLRIIRKGIHIIKKY (SEQ ID NO:3080).In certain embodiments the formulation comprises the amino acid sequenceof the C16G2 STAMP (TFFRLFNRSFTQALGKGGGKNLRIIRKGIHIIKKY, (SEQ ID NO:2).In various embodiments the targeting peptide, antimicrobial peptide,and/or a STAMP bears one or more protecting groups. In certainembodiments the protecting group(s) are independently selected from thegroup consisting of acetyl, amide, 3 to 20 carbon alkyl groups, Fmoc,Tboc, 9-fluoreneacetyl group, 1-fluorenecarboxylic group,9-florenecarboxylic group, 9-fluorenone-1-carboxylic group,benzyloxycarbonyl, Xanthyl (Xan), Trityl (Trt), 4-methyltrityl (Mtt),4-methoxytrityl (Mmt), 4-methoxy-2,3,6-trimethyl-benzenesulphonyl (Mtr),Mesitylene-2-sulphonyl (Mts), 4,4-dimethoxybenzhydryl (Mbh), Tosyl(Tos), 2,2,5,7,8-pentamethyl chroman-6-sulphonyl (Pmc), 4-methylbenzyl(MeBzl), 4-methoxybenzyl (MeOBzl), Benzyloxy (BzlO), Benzyl (Bzl),Benzoyl (Bz), 3-nitro-2-pyridinesulphenyl (Npys),1-(4,4-dimentyl-2,6-diaxocyclohexylidene)ethyl (Dde), 2,6-dichlorobenzyl(2,6-DiCl—Bzl), 2-chlorobenzyloxycarbonyl (2-Cl—Z),2-bromobenzyloxycarbonyl (2-Br—Z), Benzyloxymethyl (Bon),t-butoxycarbonyl (Boc), cyclohexyloxy (cHxO), t-butoxymethyl (Bum),t-butoxy (tBuO), t-Butyl (tBu), and Trifluoroacetyl (TFA). In certainembodiments the targeting peptide, antimicrobial peptide, and/or a STAMPis amidated at the carboxyl terminus and/or bears an acetyl group at theamino terminus. In certain embodiments the pH of the formulation rangesfrom about pH 5.0 to about pH 8.5. In certain embodiments the pH isabout pH 7.4. In various embodiments the salt is at a concentrationcomparable to that found in 1×PBS. In certain embodiments theformulation comprises PBS. In certain embodiments the formulation offurther comprising ethanol, and/or glycerin, and/or polyethylene glycol,and/or fluoride.

DEFINITIONS

The term “peptide” as used herein refers to a polymer of amino acidresidues typically ranging in length from 2 to about 50 or about 60residues. In certain embodiments the peptide ranges in length from about2, 3, 4, 5, 7, 9, 10, or 11 residues to about 60, 50, 45, 40, 45, 30,25, 20, or 15 residues. In certain embodiments the peptide ranges inlength from about 8, 9, 10, 11, or 12 residues to about 15, 20 or 25residues. In certain embodiments the amino acid residues comprising thepeptide are “L-form” amino acid residues, however, it is recognized thatin various embodiments, “D” amino acids can be incorporated into thepeptide. Peptides also include amino acid polymers in which one or moreamino acid residues is an artificial chemical analogue of acorresponding naturally occurring amino acid, as well as to naturallyoccurring amino acid polymers. In addition, the term applies to aminoacids joined by a peptide linkage or by other, “modified linkages”(e.g., where the peptide bond is replaced by an α-ester, a β-ester, athioamide, phosphonamide, carbonate, hydroxylate, and the like (see,e.g., Spatola, (1983) Chem. Biochem. Amino Acids and Proteins 7:267-357), where the amide is replaced with a saturated amine (see, e.g.,Skiles et al., U.S. Pat. No. 4,496,542, which is incorporated herein byreference, and Kaltenbronn et al., (1990) Pp. 969-970 in Proc. 11thAmerican Peptide Symposium, ESCOM Science Publishers, The Netherlands,and the like)).

The term “residue”” as used herein refers to natural, synthetic, ormodified amino acids. Various amino acid analogues include, but are notlimited to 2-aminoadipic acid, 3-aminoadipic acid, beta-alanine(beta-aminopropionic acid), 2-aminobutyric acid, 4-aminobutyric acid,piperidinic acid, δ-aminocaproic acid, 2-aminoheptanoic acid,2-aminoisobutyric acid, 3-aminoisobutyric acid, 2-aminopimelic acid, 2,4diaminobutyric acid, desmosine, 2,2′-diaminopimelic acid,2,3-diaminopropionic acid, n-ethylglycine, n-ethylasparagine,hydroxylysine, allo-hydroxylysine, 3-hydroxyproline, 4-hydroxyproline,isodesmosine, allo-isoleucine, n-methylglycine, sarcosine,n-methylisoleucine, 6-n-methyllysine, n-methylvaline, norvaline,norleucine, ornithine, and the like. These modified amino acids areillustrative and not intended to be limiting.

“β-peptides” comprise of “β amino acids”, which have their amino groupbonded to the β carbon rather than the α-carbon as in the 20 standardbiological amino acids. The only commonly naturally occurring β aminoacid is β-alanine.

Peptoids, or N-substituted glycines, are a specific subclass ofpeptidomimetics. They are closely related to their natural peptidecounterparts, but differ chemically in that their side chains areappended to nitrogen atoms along the molecule's backbone, rather than tothe α-carbons (as they are in natural amino acids).

The terms “conventional” and “natural” as applied to peptides hereinrefer to peptides, constructed only from the naturally-occurring aminoacids: Ala, Cys, Asp, Glu, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Asn,Pro, Gln, Arg, Ser, Thr, Val, Trp, and Tyr. A compound of the invention“corresponds” to a natural peptide if it elicits a biological activity(e.g., antimicrobial activity) related to the biological activity and/orspecificity of the naturally occurring peptide. The elicited activitymay be the same as, greater than or less than that of the naturalpeptide. In general, such a peptoid will have an essentiallycorresponding monomer sequence, where a natural amino acid is replacedby an N-substituted glycine derivative, if the N-substituted glycinederivative resembles the original amino acid in hydrophilicity,hydrophobicity, polarity, etc. The following are illustrative, butnon-limiting N-substituted glycine replacements:N-(1-methylprop-1-yl)glycine substituted for isoleucine (Ile),N-(prop-2-yl)glycine for valine (Val), N-benzylglycine for phenylanlaine(Phe), N-(2-hydroxyethyl)glycine for serine (Ser), and the like. Incertain embodiments substitutions need not be “exact”. Thus for example,in certain embodiments N-(2-hydroxyethyl)glycine may substitute for Ser,Thr, Cys, and/or Met; N-(2-methylprop-1-yl)glycine may substitute forVal, Leu, and/or Ile. In certain embodiments N-(2-hydroxyethyl)glycinecan be used to substitute for Thr and Ser, despite the structuraldifferences: the side chain in N-(2-hydroxyethyl)glycine is onemethylene group longer than that of Ser, and differs from Thr in thesite of hydroxy-substitution. In general, one may use anN-hydroxyalkyl-substituted glycine to substitute for any polar aminoacid, an N-benzyl- or N-aralkyl-substituted glycine to replace anyaromatic amino acid (e.g., Phe, Trp, etc.), an N-alkyl-substitutedglycine such as N-butylglycine to replace any nonpolar amino acid (e.g.,Leu, Val, Ile, etc.), and an N-(aminoalkyl)glycine derivative to replaceany basic polar amino acid (e.g., Lys and Arg).

Where an amino acid sequence is provided herein, L-, D-, or beta aminoacid versions of the sequence are also contemplated as well as retro,inversion, and retro-inversion isoforms. In addition, conservativesubstitutions (e.g., in the binding peptide, and/or antimicrobialpeptide, and/or linker peptide) are contemplated. Non-protein backbones,such as PEG, alkane, ethylene bridged, ester backbones, and otherbackbones are also contemplated. Also fragments ranging in length fromabout 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22,23, 24, or 25 amino acids up to the full length minus one amino acid ofthe peptide are contemplated where the fragment retains at least 50%,preferably at least 60% 70% or 80%, more preferably at least 90%, 95%,98%, 99%, or at least 100% of the activity (e.g., binding specificityand/or avidity, antimicrobial activity, etc.) of the full length peptideare contemplated.

A “compound antimicrobial peptide” or “compound AMP” refers to aconstruct comprising two or more AMPs joined together. The AMPs can bejoined directly or through a linker. They can be chemically conjugatedor, where joined directly together or through a peptide linker cancomprise a fusion protein.

In certain embodiments, conservative substitutions of the amino acidscomprising any of the sequences described herein are contemplated. Invarious embodiments one, two, three, four, or five different residuesare substituted. The term “conservative substitution” is used to reflectamino acid substitutions that do not substantially alter the activity(e.g., antimicrobial activity and/or specificity) of the molecule.Typically conservative amino acid substitutions involve substitution oneamino acid for another amino acid with similar chemical properties (e.g.charge or hydrophobicity). Certain conservative substitutions include“analog substitutions” where a standard amino acid is replaced by anon-standard (e.g., rare, synthetic, etc) amino acid differing minimallyfrom the parental residue. Amino acid analogs are considered to bederived synthetically from the standard amino acids without sufficientchange to the structure of the parent, are isomers, or are metaboliteprecursors. Examples of such “analog substitutions” include, but are notlimited to, 1) Lys-Orn, 2) Leu-Norleucine, 3) Lys-Lys[TFA], 4)Phe-Phe[Gly], and 5) δ-amino butylglycine-ξ-amino hexylglycine, wherePhe[gly] refers to phenylglycine (a Phe derivative with a H rather thanCH₃ component in the R group), and Lys[TFA] refers to a Lys where anegatively charged ion (e.g., TFA) is attached to the amine R group.Other conservative substitutions include “functional substitutions”where the general chemistries of the two residues are similar, and canbe sufficient to mimic or partially recover the function of the nativepeptide. Strong functional substitutions include, but are not limitedto 1) Gly/Ala, 2) Arg/Lys, 3) Ser/Tyr/Thr, 4) Leu/Ile/Val, 5) Asp/Glu,6) Gln/Asn, and 7) Phe/Trp/Tyr, while other functional substitutionsinclude, but are not limited to 8) Gly/Ala/Pro, 9) Tyr/His, 10)Arg/Lys/His, 11) Ser/Thr/Cys, 12) Leu/Ile/Val/Met, and 13) Met/Lys(special case under hydrophobic conditions). Various “broad conservativesubstations” include substitutions where amino acids replace other aminoacids from the same biochemical or biophysical grouping. This issimilarity at a basic level and stems from efforts to classify theoriginal 20 natural amino acids. Such substitutions include 1) nonpolarside chains: Gly/Ala/Val/Leu/Ile/Met/Pro/Phe/Trp, and/or 2) unchargedpolar side chains Ser/Thr/Asn/Gln/Tyr/Cys. In certain embodimentsbroad-level substitutions can also occur as paired substitutions. Forexample, Any hydrophilic neutral pair [Ser, Thr, Gln, Asn, Tyr,Cys]+[Ser, Thr, Gln, Asn, Tyr, Cys] can may be replaced by acharge-neutral charged pair [Arg, Lys, His]+[Asp, Glu]. The followingsix groups each contain amino acids that, in certain embodiments, aretypical conservative substitutions for one another: 1) Alanine (A),Serine (S), Threonine (T); 2) Aspartic acid (D), Glutamic acid (E); 3)Asparagine (N), Glutamine (Q); 4) Arginine (R), Lysine (K), Histidine(H); 5) Isoleucine (I), Leucine (L), Methionine (M), Valine (V); and 6)Phenylalanine (F), Tyrosine (Y), Tryptophan (W). Where amino acidsequences are disclosed herein, amino acid sequences comprising, one ormore of the above-identified conservative substitutions are alsocontemplated.

In certain embodiments, targeting peptides, antimicrobial peptides,and/or STAMPs compromising at least 80%, preferably at least 85% or 90%,and more preferably at least 95% or 98% sequence identity with any ofthe sequences described herein are also contemplated. The terms“identical” or percent “identity,” refer to two or more sequences thatare the same or have a specified percentage of amino acid residues thatare the same, when compared and aligned for maximum correspondence, asmeasured using one of the following sequence comparison algorithms or byvisual inspection. With respect to the peptides of this inventionsequence identity is determined over the full length of the peptide. Forsequence comparison, typically one sequence acts as a referencesequence, to which test sequences are compared. When using a sequencecomparison algorithm, test and reference sequences are input into acomputer, subsequence coordinates are designated, if necessary, andsequence algorithm program parameters are designated. The sequencecomparison algorithm then calculates the percent sequence identity forthe test sequence(s) relative to the reference sequence, based on thedesignated program parameters. Optimal alignment of sequences forcomparison can be conducted, e.g., by the local homology algorithm ofSmith & Waterman (1981) Adv. Appl. Math. 2: 482, by the homologyalignment algorithm of Needleman & Wunsch (1970) J. Mol. Biol. 48: 443,by the search for similarity method of Pearson & Lipman (1988) Proc.Natl. Acad. Sci., USA, 85: 2444, by computerized implementations ofthese algorithms (GAP, BESTFIT, FASTA, and TFASTA in the WisconsinGenetics Software Package, Genetics Computer Group, 575 Science Dr.,Madison, Wis.), or by visual inspection.

The term “specificity” when used with respect to the antimicrobialactivity of a peptide indicates that the peptide preferentially inhibitsgrowth and/or proliferation and/or kills a particular microbial speciesas compared to other related and/or unrelated microbes. In certainembodiments the preferential inhibition or killing is at least 10%greater (e.g., LD₅₀ is 10% lower), preferably at least 20%, 30%, 40%, or50%, more preferably at least 2-fold, at least 5-fold, or at least10-fold greater for the target species.

“Treating” or “treatment” of a condition as used herein may refer topreventing the condition, slowing the onset or rate of development ofthe condition, reducing the risk of developing the condition, preventingor delaying the development of symptoms associated with the condition,reducing or ending symptoms associated with the condition, generating acomplete or partial regression of the condition, or some combinationthereof.

The term “consisting essentially of” when used with respect to anantimicrobial peptide (AMP) or AMP motif as described herein, indicatesthat the peptide or peptides encompassed by the library or variants,analogues, or derivatives thereof possess substantially the same orgreater antimicrobial activity and/or specificity as the referencedpeptide. In certain embodiments substantially the same or greaterantimicrobial activity indicates at least 80%, preferably at least 90%,and more preferably at least 95% of the anti microbial activity of thereferenced peptide(s) against a particular bacterial species (e.g., S.mutans).

The term “porphyrinic macrocycle” refers to a porphyrin or porphyrinderivative. Such derivatives include porphyrins with extra ringsortho-fused, or orthoperifused, to the porphyrin nucleus, porphyrinshaving a replacement of one or more carbon atoms of the porphyrin ringby an atom of another element (skeletal replacement), derivatives havinga replacement of a nitrogen atom of the porphyrin ring by an atom ofanother element (skeletal replacement of nitrogen), derivatives havingsubstituents other than hydrogen located at the peripheral (meso-,.beta.-) or core atoms of the porphyrin, derivatives with saturation ofone or more bonds of the porphyrin (hydroporphyrins, e.g., chlorins,bacteriochlorins, isobacteriochlorins, decahydroporphyrins, corphins,pyrrocorphins, etc.), derivatives obtained by coordination of one ormore metals to one or more porphyrin atoms (metalloporphyrins),derivatives having one or more atoms, including pyrrolic andpyrromethenyl units, inserted in the porphyrin ring (expandedporphyrins), derivatives having one or more groups removed from theporphyrin ring (contracted porphyrins, e.g., corrin, corrole) andcombinations of the foregoing derivatives (e.g. phthalocyanines,porphyrazines, naphthalocyanines, subphthalocyanines, and porphyrinisomers). Certain porphyrinic macrocycles comprise at least one5-membered ring.

As used herein, an “antibody” refers to a protein consisting of one ormore polypeptides substantially encoded by immunoglobulin genes orfragments of immunoglobulin genes. The recognized immunoglobulin genesinclude the kappa, lambda, alpha, gamma, delta, epsilon and mu constantregion genes, as well as myriad immunoglobulin variable region genes.Light chains are classified as either kappa or lambda. Heavy chains areclassified as gamma, mu, alpha, delta, or epsilon, which in turn definethe immunoglobulin classes, IgG, IgM, IgA, IgD and IgE, respectively.

A typical immunoglobulin (antibody) structural unit is known to comprisea tetramer. Each tetramer is composed of two identical pairs ofpolypeptide chains, each pair having one “light” (about 25 kD) and one“heavy” chain (about 50-70 kD). The N-terminus of each chain defines avariable region of about 100 to 110 or more amino acids primarilyresponsible for antigen recognition. The terms variable light chain(V_(L)) and variable heavy chain (V_(H)) refer to these light and heavychains respectively.

Antibodies exist as intact immunoglobulins or as a number of wellcharacterized fragments produced by digestion with various peptidases.Thus, for example, pepsin digests an antibody below the disulfidelinkages in the hinge region to produce F(ab)′₂, a dimer of Fab whichitself is a light chain joined to V_(H)-C_(H)1 by a disulfide bond. TheF(ab)′₂ may be reduced under mild conditions to break the disulfidelinkage in the hinge region thereby converting the (Fab′)₂ dimer into anFab′ monomer. The Fab′ monomer is essentially an Fab with part of thehinge region (see, Fundamental Immunology, W. E. Paul, ed., Raven Press,N.Y. (1993), for a more detailed description of other antibodyfragments). While various antibody fragments are defined in terms of thedigestion of an intact antibody, one of skill will appreciate that suchFab′ fragments may be synthesized de novo either chemically or byutilizing recombinant DNA methodology. Thus, the term antibody, as usedherein also includes antibody fragments either produced by themodification of whole antibodies or synthesized de novo usingrecombinant DNA methodologies, including, but are not limited to, Fab′₂,IgG, IgM, IgA, scFv, dAb, nanobodies, unibodies, and diabodies.

In certain embodiments antibodies and fragments of the present inventioncan be bispecific. Bispecific antibodies or fragments can be of severalconfigurations. For example, bispecific antibodies may resemble singleantibodies (or antibody fragments) but have two different antigenbinding sites (variable regions). In various embodiments bispecificantibodies can be produced by chemical techniques (Kranz et al.(1981)Proc. Natl. Acad. Sci., USA, 78: 5807), by “polydoma” techniques(see, e.g., U.S. Pat. No. 4,474,893), or by recombinant DNA techniques.In certain embodiments bispecific antibodies of the present inventioncan have binding specificities for at least two different epitopes, atleast one of which is an epitope of a microbial organism. The microbialbinding antibodies and fragments can also be heteroantibodies.Heteroantibodies are two or more antibodies, or antibody bindingfragments (e.g., Fab) linked together, each antibody or fragment havinga different specificity.

The term “STAMP” refers to Specifically Targeted Anti-MicrobialPeptides. In various embodiments, a STAMP comprises one or more peptidetargeting moieties attached to one or more antimicrobial moieties (e.g.,antimicrobial peptides (AMPs)). An MH-STAMP is a STAMP bearing two ormore targeting domains (i.e., a multi-headed STAMP).

The terms “isolated” “purified” or “biologically pure” refer to materialwhich is substantially or essentially free from components that normallyaccompany it as found in its native state. In the case of a peptide, anisolated (naturally occurring) peptide is typically substantially freeof components with which it is associated in the cell, tissue, ororganism. The term isolated also indicates that the peptide is notpresent in a phage display, yeast display, or other peptide library.

In various embodiments the amino acid abbreviations shown in Table 1 areused herein.

TABLE 1 Amino acid abbreviations. Abbreviation Name 3 Letter 1 LetterAlanine Ala A βAlanine (NH₂—CH₂—CH₂—COOH) βAla Arginine Arg R AsparagineAsn N Aspartic Acid Asp D Cysteine Cys C Glutamic Acid Glu E GlutamineGln Q Glycine Gly G Histidine His H Homoserine Hse — Isoleucine Ile ILeucine Leu L Lysine Lys K Methionine Met M Methionine sulfoxide Met (O)— Methionine methylsulfonium Met (S-Me) — Norleucine Nle — PhenylalaninePhe F Proline Pro P Serine Ser S Threonine Thr T Tryptophan Trp WTyrosine Tyr Y Valine Val V episilon-aminocaproic acid Ahx J(NH²—(CH₂)₅—COOH) 4-aminobutanoic acid gAbu (NH₂—(CH₂)₃—COOH)tetrahydroisoquinoline-3- O carboxylic acidLys(N(epsilon)-trifluoroacetyl) K[TFA] α-aminoisobutyric acid Aib B

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows some illustrative porphyrins (compounds 92-99) suitable foruse as targeting moieties and/or antimicrobial effectors.

FIG. 2 shows some illustrative porphyrins (compounds 100-118) suitablefor use as targeting moieties and/or antimicrobial effectors.

FIG. 3 shows some illustrative porphyrins (in particularphthalocyanines) (compounds 119-128) suitable for use as targetingmoieties and/or antimicrobial effectors.

FIG. 4 illustrates the structures of two phthalocyanines, MonoastralFast Blue B and Monoastral Fast Blue G suitable for use as targetingmoieties and/or antimicrobial effectors.

FIG. 5 illustrates certain azine photosensitizers suitable for use astargeting moieties and/or antimicrobial effectors in the compositionsand methods described herein.

FIG. 6 shows illustrative cyanine suitable for use as targeting moietiesand/or antimicrobial effectors in the compositions and methods describedherein.

FIG. 7 shows illustrative psoralen (angelicin) photosensitizers suitablefor use as targeting moieties and/or antimicrobial effectors in thecompositions and methods described herein.

FIG. 8 shows illustrative hypericin and the perylenequinonoid pigmentssuitable for use as targeting moieties and/or antimicrobial effectors inthe compositions and methods described herein.

FIG. 9 shows illustrative acridines suitable for use as targetingmoieties and/or antimicrobial effectors in the compositions and methodsdescribed herein.

FIG. 10 illustrates the structure of the acridine Rose Bengal.

FIG. 11 illustrates various crown ethers suitable for use as targetingmoieties and/or antimicrobial effectors in the compositions and methodsdescribed herein.

FIG. 12 illustrates the structure of cumin.

FIG. 13 illustrates an example of a targeted light-activated porphyrinwe have constructed: C16-P18 comprising a porphyrin coupled to a C16(SEQ ID NO:3) targeting sequence.

FIG. 14 schematically shows some illustrative configurations forchimeric constructs described herein. A: Shows a single targeting moietyT1 attached to a single effector E1 by a linker/spacer L. B: Showsmultiple targeting moieties T1, T2, T3 attached directly to each otherand attached by a linker L to a single effector E1. In variousembodiments T1, T2, and T3, can be domains in a fusion protein. C: Showsmultiple targeting moieties T1, T2, T3 attached to each other by linkersL and attached by a linker L to a single effector E1. In variousembodiments T1, T2, and T3, can be domains in a fusion protein. D: Showsa single targeting moiety T1 attached by a linker L to multipleeffectors E1, E2, and E3 joined directly to each other. E: Shows asingle targeting moiety T1 attached by a linker L to multiple effectorsE1, E2, and E3 joined to each other by linkers L. F: Shows multipletargeting moieties joined directly to each other and by a linker L tomultiple effectors joined to each other by linkers L. G: Shows multipletargeting moieties joined to each other by linkers L and by a linker Lto multiple effectors joined to each other by linkers L. In variousembodiments T1, T2, and T3, and/or E1, E2, and E3 can be domains in afusion protein. H: Illustrates a branched configuration where multipletargeting moieties are linked to a single effector. I: Illustrates adual branched configuration where multiple targeting moieties are linkedto multiple effectors. J: Illustrates a branched configuration wheremultiple targeting moieties are linked to multiple effectors where theeffectors are joined to each other in a linear configuration.

FIG. 15 illustrates various MH-STAMPs used in Example 1. The design,sequence, and observed mass (m/z) for M8(KH)-20 (SEQ ID NOs:4, 5, and6), BL(KH)-20 (SEQ ID 7, 8, and 9), and M8(BL)-20 (SEQ ID 10, 11, and12).

FIGS. 16A and 16B show HPLC and MS spectra of M8(KH)-20. The quality ofthe completed MH-STAMP was analyzed by HPLC (FIG. 16A) and MALDI massspectroscopy (FIG. 16B). At UV absorbance 215 nm (260 and 280 nm arealso plotted), a single major product was detected by HPLC (* retentionvolume 11.04 mL). After fraction collection, the correct mass (m/z) forsingle-charged M8(KH)-20, 4884.91 (marked by *), was observed for thispeak. Y-axis: 16A, mAU miliabsorbance units; 16B, percent intensity.

FIG. 17A-17E show growth inhibitory activity of MH-STAMPs. Monoculturesof S. mutans (FIG. 17A); P. aeruginosa (FIG. 17B); S. epidermidis (FIG.17C); S. aureus (FIG. 17D); or E. coli (FIG. 17E); were treated withpeptides (as indicated in the figure) for 10 min. Agent was then removedand fresh media returned. Culture recovery was measured over time(OD600). Plots represent the average of at least 3 independentexperiments with standard deviations.

FIG. 18 illustrates the selective activity of dual-targeted andsingle-targeted MH-STAMPs in mixed culture. A mixture of P. aeruginosa(Pa), S. mutans (Sm), E. coli (Ec), and S. epidermidis (Se) planktoniccells were mixed with MH-STAMPs (as indicated in the figure) and treated24 h. After incubation, cfu/mL of remaining constituent species werequantitated after plating to selective media. * indicates under 200surviving cfu/mL recovered.

FIGS. 19A and 19B illustrate Rose Bengal (FIG. 19A) and synthesis schemefor C16-RB, halides and side-chains omitted for clarity (FIG. 19B).

FIG. 20 shows LC/MS profile C16-RB. Purity and molecular mass of C16-RBwas confirmed by LC/MS. A single product was observed at 11.92 min withmass species at 1040.8 and 1560.25 daltons. Expected C16-RB mas:m/z=3118, m²⁺/z=1559, m³⁺/Z=1039.

FIG. 21 illustrates activity of RB and C16-RB against single-species S.mutans biofilms. * indicates fewer than 100 cfu/mL recovered

FIG. 22 shows S. mutans-specific C16-RB activity. C16-RB, and not RBalone, preferentially eliminated S. mutans, and not other oralstreptococci, after blue light illumination.

DETAILED DESCRIPTION

In various embodiments, novel “targeting” peptides are identified thatspecifically or preferentially bind particular microorganisms (e.g.,bacteria, yeasts, fungi, etc.). These peptides can be used alone tobind/capture and thereby identify and/or isolate particular targetmicroorganisms, or they can be attached to one or more effectors (e.g.,drugs, labels, etc.) and used as targeting moieties thereby providing achimeric moiety that preferentially or specifically delivers theeffector to a target microorganism, a population of targetmicroorganisms, a microbial film, a biofilm, and the like.

In various embodiments novel peptides having antimicrobial activityagainst certain bacteria, fungi, yeasts, and/or viruses and/or havingactivity that inhibits the growth or maintenance of biofilms comprisingsuch microorganisms are provided. The AMPs can be used to inhibit thegrowth and/or proliferation of a microbial species and/or the growthand/formation and/or maintenance of a biofilm comprising the microbialspecies.

In certain embodiments, the targeting moieties can be attached toantimicrobial peptides to form Specifically Targeted Anti-MicrobialPeptides (STAMPs). In certain embodiments attachment of one or moretargeting moieties/peptides to one or more antimicrobial peptides cannarrow the spectrum of activity of the AMP(s) to provide efficacyagainst one or a few target microorganisms without substantiallydisrupting the remaining microbial ecology and thereby provide increasedefficacy with fewer side effects.

In certain embodiments STAMPs or effector peptides can be deliveredagainst pathogenic bacteria by being cloned and expressed in probioticorganisms for therapeutic delivery in vivo. Recombinant expression (andoverexpression) and export of antimicrobial peptides and other peptidesare well documented in bacteria, including species that are alsoutilized as probiotics.

In various embodiments the targeting peptides, antimicrobial peptides,and/or STAMPs can be formulated individually, in combination with eachother, in combination with other antimicrobial peptides, and/or incombination with various antibacterial agents to provide antimicrobialreagents and/or pharmaceuticals.

Accordingly, in certain embodiments this invention provides peptideshaving antimicrobial activity, compositions comprising the peptides,methods of using the peptides (or compositions thereof) to inhibit thegrowth of or kill a wide variety of microbial targets and methods ofusing the peptides (or compositions thereof) to treat or preventmicrobial infections and diseases related thereto in both plants andanimals.

The various peptides (targeting peptides, AMPs, STAMPs, etc.) describedherein exhibit antimicrobial activity, being biostatic or biocidalagainst a certain microbial targets, including but not limited to,Gram-negative bacteria such as Acinetobacter baumannii, Escherichiacoli, Fusobacterium nucleatum, Pseudomonas aeruginosa, Porphyromonasgingivalis; Gram-positive bacteria such as Actinomyces naeslundii,Bacillus subtilis, Clostridium difficile, Enterococcus faecalis,Staphylococcus aureus (and MRSA), S. epidermidis, Streptococcus mutans,Streptococcus pneumoniae; and yeast or fungi such as Aspergillus niger,Candida albicans, Malassezia furfur, and Trichophyton rubrum (see, e.g.,Table 2). Significantly, various peptides described herein are biostaticor biocidal against clinically relevant pathogens exhibiting multi-drugresistance such as, for example, methicillin-resistant Staphylococcusaureus (“MRSA”).

TABLE 2 Illustrative target microorganisms and associated pathology.Acinetobacter baumannii Pathogenic gram-negative bacillus that isnaturally sensitive (A. baumannii) to relatively few antibiotics.Actinomyces naeslundii Gram positive rod shaped bacteria that occupy theoral (A. naeslundii) cavity and are implicated in periodontal diseaseand root caries. Aspergillus niger A fungal infection that often causesa black mould to appear (A. niger) on some fruit and vegetables but mayalso infect humans through inhalation of fungal spores. Bacteroidesfragilis Gram positive bacilli that are opportunistic human (B.fragilis) pathogens, causing infections of the peritoneal cavity,gastrointestinal surgery, and appendicitis via abscess formation,inhibiting phagocytosis. Resistant to a wide variety of antibiotics -β-lactams, aminoglycosides, and recently many species have acquiredresistance to erythromycin and tetracycline. Bacillus subtilisGram-positive, catalase-positive bacterium. (B. subtilis) Candidaalbicans Causal agent of opportunistic oral and genital fungal (C.albicans) infections in humans. Clostridium difficile A gram-positive,anaerobic, spore-forming bacillus that is (C. difficile) responsible forthe development of antibiotic-associated diarrhea and colitis.Corynebacterium jeikeium Gram positive, opportunistic pathogen primarilyof (C. jeikeium) immunocompromised (neutropenic) patients. Highlyresistant to antibiotics Campylobacter jejuni Gram negative cause ofhuman gastroenteritis/food (C. jejuni) poisoning. Escherichia coli Gramnegative rod-shaped bacterium commonly found in the (E. coli) lowerintestine of warm-blooded organisms. Certain strains cause serious foodpoisoning in humans. Enterococcus faecalis Gram-positive commensalbacterium (E. faecalis) Fusobacterium nucleatum Gram negativeschizomycetes bacterium often seen in (F. nucleatum) necrotic tissue andimplicated, but not conclusively, with other organisms in the causationand perpetuation of periodontal disease. Lactobacillus acidophilusGram-positive commensal bacterium. (L. acidophilus) Legionellapneumophila Gram negative bacterium that is the causative agent of (L.pneumophila) legionellosis or Legionnaires' disease. (Micrococcusluteus) Gram positive, spherical, saprotrophic bacterium found in M.luteus soil, dust, water and air, and as part of the normal flora of themammalian skin. The bacterium also colonizes the human mouth, mucosae,oropharynx and upper respiratory tract. Considered an emergingnosocomial pathogen in immunocompromised patients. Mycobacteriumsmegmatis Gram-variable (acid-fast) soil-dwelling organism utilized as(M. smegmatis) a proxy for Mycobacterium tuberculosis during researchand development. Malassezia furfur Yeast - cutaneous pathogen. (M.furfur) Methicillin-resistant Any strain of Staphylococcus aureusbacteria (gram positive) Staphylococcus aureus that is resistant to aone or more members of a large group of (MRSA) antibiotics called thebeta-lactams. Responsible for skin and systemic infections. Myxococcusxanthus Gram negative cells that form biofilms and display primitive (M.xanthus) social motility and fruiting body organization. Pseudomonasaeruginosa Gram-negative rod. Frequent opportunistic pathogen and P.aeruginosa infects burn wounds. Causes ear infections in children.Infects the lungs of cystic fibrosis patients. Porphyromonas gingivalisNon-motile, gram-negative, rod-shaped, anaerobic (P. gingivalis)pathogenic bacterium (periodontal disease) ProgeussmirabilisGram-negative, facultatively anaerobic bacterium. Causes (P. mirabilis)90% of all ‘Proteus’ infections in humans. S. epidermidis Gram-positive,coagulase-negative cocci. Nosocomial (S. epidermidis) pathogenassociated with infection (biofilm) of implanted medical device.Streptococcus mutans Gram-positive, facultatively anaerobic bacteriumcommonly (S. mutans) found in the human oral cavity and is a significantcontributor to tooth decay Streptococcus pneumoniae Gram-positive,alpha-hemolytic, bile soluble aerotolerant (S. pneumoniae) anaerobe.Causal agent for streptococcal pneumonia. Treponema denticolaGram-negative oral spirochete associated with the incidence (T.denticola) and severity of human periodontal disease. Trichophytonrubrum Most common cause of athlete's foot, jock itch and (T. rubrum)ringworm.

The various agents described herein (targeting peptides, compoundtargeting peptides, antimicrobial peptides (AMPs) and/or compound AMPs,STAMPs and/or other chimeric moieties). or compositions thereof, areuseful as biocidal or biostatic or fungicidal or fungistatic agentsand/or virucidal agents in a wide variety of applications. For example,the agents can be used to disinfect or preserve a variety of materialsincluding medical instruments, foodstuffs, medicaments, cosmetics andother nutrient-containing materials. Various peptides described hereinare particularly useful as bacteriostatic or bactericidal agents againstmulti-drug-resistant pathogens such as MRSA in a variety of clinicalsettings.

The agents described herein, or compositions thereof, are also usefulfor the prophylaxis or treatment of microbial infections and diseasesrelated thereto in both plants and animals. Such diseases include, butare not limited to, Gram-negative and Gram-positive bacterialinfections, endocarditis, pneumonia and other respiratory infections,urinary tract infections, systemic candidiasis, oral mucositis, fungalinfections, biofilm formation or maintenance (e.g., on medicalimplants), and the like.

In various embodiments, the agents described herein can be formulatedindividually, in combination with each other, in combination with otherantimicrobial peptides, and/or in combination with various antibiotic(e.g., antibacterial) agents in “home healthcare” formulations. Suchformulations include, but are not limited to toothpaste, mouthwash,tooth whitening strips or solutions, contact lens storage, wetting, orcleaning solutions, dental floss, toothpicks, toothbrush bristles, oralsprays, oral lozenges, nasal sprays, aerosolizers for oral and/or nasalapplication, wound dressings (e.g., bandages), and the like.

Such applications are illustrative and not limiting. Using the teachingsprovided herein other uses of the AMPs and compositions described hereinwill be recognized by one of

I. Targeting Peptides.

A) Uses of Targeting Peptides.

The novel microorganism-binding peptides (targeting peptides) describedherein can be used to preferentially or specifically deliver an effectorto a microorganism (e.g., a bacterium, a fungus, a protozoan, an algae,etc.), to a bacterial film, to a biofilm, and the like. The targetingpeptides described herein can be used to bind to and thereby labelparticular targets, and/or as capture reagents to bind targetmicroorganisms and thereby provide an indicator of the presence and/orquantity of the target microorganism(s). In certain embodiments thetargeting peptide can be attached to an effector such as an epitope tagand/or a detectable label and thereby facilitate the identification ofthe presence and/or location, and/or quantity of the target (e.g.,target organism). Thus targeting moieties are thus readily adapted foruse in in vivo diagnostics, and/or ex vivo assays. Moreover, because ofsmall size and good stability, microorganism binding peptides are wellsuited for microassay systems (e.g., microfluidic assays (Lab on aChip), microarray assays, and the like).

In certain embodiments the microorganism binding peptides (targetingpeptides) can be attached to an effector that has antimicrobial activity(e.g., an antimicrobial peptide, an antibacterial and/or antifungal, avehicle that contains an antibacterial or antifungal, etc. In variousembodiments these chimeric moieties can be used in vivo, or ex vivo topreferentially inhibit or kill the target organism(s).

In certain embodiments the targeting peptides can be recombinantlyexpressed as part of a yeast or phage tail fiber or coat protein toenhance binding of the yeast or phage to a specific bacterialGram-designation, genus, species, or strain. Phage with expressedpeptides will then display altered infection selectivity towards adesigned target bacteria for use in phage therapy. Cloning the DNAencoding a peptide of interest into the major or minor coat proteins ofa bacteriophage, for example in Proteins I through VIII of phages SAP-2,M13, or T7, will result in a targeted phage expressing 1-200 copies ofthe targeting peptide on the phage surface.

In certain embodiments the targeting peptides can be used in variouspre-targeting protocols. In pre-targeting protocols, a chimeric moleculeis utilized comprising a primary targeting species (e.g. amicroorganism-binding peptide) that specifically binds the desiredtarget (e.g. a bacterium) and an effector that provides a binding sitethat is available for binding by a subsequently administered secondtargeting species. Once sufficient accretion of the primary targetingspecies (the chimeric molecule) is achieved, a second targeting speciescomprising (i) a diagnostic or therapeutic agent and (ii) a secondtargeting moiety, that recognizes the available binding site of theprimary targeting species, is administered.

An illustrative example of a pre-targeting protocol is the biotin-avidinsystem for administering a cytotoxic radionuclide to a tumor. In atypical procedure, a monoclonal antibody targeted against atumor-associated antigen is conjugated to avidin and administered to apatient who has a tumor recognized by the antibody. Then the therapeuticagent, e.g., a chelated radionuclide covalently bound to biotin, isadministered. The radionuclide, via its attached biotin is taken up bythe antibody-avidin conjugate pretargeted at the tumor. Examples ofpre-targeting biotin/avidin protocols are described, for example, inGoodwin et al., U.S. Pat. No. 4,863,713; Goodwin et al. (1988) J. Nucl.Med. 29: 226; Hnatowich et al. (1987) J. Nucl. Med. 28: 1294; Oehr etal. (1988) J. Nucl. Med. 29: 728; Klibanov et al. (1988) J. Nucl. Med.29: 1951; Sinitsyn et al. (1989) J. Nucl. Med. 30: 66; Kalofonos et al.(1990) J. Nucl. Med. 31: 1791; Schechter et al. (1991) Int. J. Cancer48:167; Paganelli et al. (1991) Cancer Res. 51: 5960; Paganelli et al.(1991) Nucl. Med. Commun. 12: 211; Stickney et al. (1991) Cancer Res.51: 6650; and Yuan et al. (1991) Cancer Res. 51:3119.

It will be recognized that the tumor-specific antibody used for cancertreatments can be replaced with a microorganism binding peptide of thepresent invention and similar pre-targeting strategies can be used todirect labels, antibiotics, and the like to the target organism(s).

Three-step pre-targeting protocols in which a clearing agent isadministered after the first targeting composition has localized at thetarget site also have been described. The clearing agent binds andremoves circulating primary conjugate which is not bound at the targetsite, and prevents circulating primary targeting species(antibody-avidin or conjugate, for example) from interfering with thetargeting of active agent species (biotin-active agent conjugate) at thetarget site by competing for the binding sites on the activeagent-conjugate. When antibody-avidin is used as the primary targetingmoiety, excess circulating conjugate can be cleared by injecting abiotinylated polymer such as biotinylated human serum albumin. This typeof agent forms a high molecular weight species with the circulatingavidin-antibody conjugate which is quickly recognized by thehepatobiliary system and deposited primarily in the liver.

Examples of these protocols are disclosed, e.g., in PCT Application No.WO 93/25240; Paganelli et al. (1991) Nucl. Med. Comm., 12: 211-234; Oehret al. (1988) J. Nucl. Med., 29: 728-729; Kalofonos et al. (1990) J.Nucl. Med., 31: 1791-1796; Goodwin et al. (1988) J. Nucl. Med., 29:226-234; and the like).

These applications of microorganism binding peptides of this inventionare intended to be illustrative and not limiting. Using the teachingprovided herein, other uses will be recognized by one of skill in theart.

B) Illustrative Novel Targeting Peptides.

In certain embodiments, the targeting moiety comprises one or moretargeting peptides that bind particular bacteria, fungi, and/or yeasts,and/or algae, and/or viruses and/or that bind particular groups ofbacteria, and/or groups of fungi, and/or groups of yeasts, and/or groupsof algae.

In certain embodiments the targeting peptides include peptidescomprising or consisting of one or more of the amino acid sequencesshown in Table 3 (SEQ ID NOs:13-1566). In various embodiments thepeptides include peptides comprising or consisting of the retro,inverso, retro-inverso, and/or beta form of one or more of the aminoacid sequences shown in Table 3. Also contemplated are circularpermutations of these sequences as well as peptides comprising orconsisting of the retro, inverso, retro-inverso, and/or beta form ofsuch circular permutations.

It will also be recognized, that in certain embodiments, any peptide orcompound AMP described herein can be circularized.

In various embodiments the peptides can optionally bear one or moreprotecting groups, e.g., and the amino and/or carboxyl termini, and/oron side chains.

Also contemplated are peptides comprising one, two, three four, or fiveconservative substitutions of these amino acid sequences.

TABLE 3 Illustrative list of novel targeting peptides. SEQ ID IDTarget(s) Targeting Peptide Sequence NO 1T-3 S. mutansVLGIAGGLDAYGELVGGN 13 S. gordonii 1T-4 S. mutans LDAYGELVGGN 14 S.gordonii S. sanguinis S. oxalis V. atypica L. casei 1T-6 S. mutansKFINGVLSQFVLERK 15 1T-7 M. xanthus SQRIIEPVKSPQPYPGFSVS 16 1T-8 M.xanthus FSVAACGEQRAVTFVLLIEDLI 17 1T-9 M. xanthusWAWAESPRCVSTRSNIHALAFRVEVAA 18 LT 1T-10 M. xanthus SPAGLPGDGDEA 19 1T-11S. mutans RISE 20 S. epidermidis P. aeruginosa 1T-12 C. xerosisFGNIFKGLKDVIETIVKWTAAK 21 C. striatum S. epidermidis S. mutans 1T-13 S.aureus FRSPCINNNSLQPPGVYPAR 22 S. epidermidis P. aeruginosa 1T-14 S.mutans ALAGLAGLISGK 23 S. aureus S. epidermidis C. xerosis 1T-15 S.mutans DVILRVEAQ 24 1T-16 P. aeruginosa IDMR 25 1T-17 S. mutans NNAIVYIS26 1T-18 S. aureus YSKTLHFAD 27 S. epidermidis C. striatum P. aeruginosa1T-19 S. aureus PGAFRNPQMPRG 28 S. epidermidis P. aeruginosa 1T-20 S.mutans PALVDLSNKEAVWAVLDDHS 29 P. aeruginosa 1T-21 S. mutansYVEEAVRAALKKEARISTEDTPVNLPSF 30 P. aeruginosa DC 1T-22 S. epidermidisVPLDDGTRRPEVARNRDKDRED 31 P. aeruginosa 1T-23 S. mutansPALVDLSNKEAVWAVLDDHS 32 P. aeruginosa 1T-24 P. aeruginosaEEAEEKLAEVSQAVKRLVR 33 1T-25 S. aureus VGLDVSVLVLFFGLQLLSVLLGAMIR 34 S.epidermidis C. xerosis C. striatum P. aeruginosa 1T-26 S. mutansLTILPTTFFAIIVPILAVAFIAYSGFKIKGI 35 S. aureus VEHKDQW S. epidermidis C.jeikeium C. xerosis C. striatum P. aeruginosa 1T-27 S. mutansALFVSLEQFLVVVAKSVFALCHSGTLS 36 S. aureus S. epidermidis C. jeikeium C.xerosis C. striatum P. aeruginosa 1T-28 P. aeruginosaVSRDEAMEFIDREWTTLQPAGKSHA 37 1T-29 S. mutans GSVIKKRRKRMSKKKHRKMLRRTRVQ38 S. aureus RRKLGK S. epidermidis C. jeikeium C. xerosis C. striatum P.aeruginosa 1T-30 S. aureus GKAKPYQVRQVLRAVDKLETRRKKGGR 39 S. epidermidisC. xerosis C. striatum P. aeruginosa 1T-31 S. mutans NATGTDIGEVTLTLGRFS40 P. aeruginosa 1T-32 S. mutans VSFLAGWLCLGLAAWRLGNA 41 1T-33 S. aureusVRTLTILVIFIFNYLKSISYKLKQPFENNL 42 S. epidermidis AQSMISI C. jeikeium C.xerosis C. striatum P. aeruginosa 1T-34 S. aureusAFWLNILLTLLGYIPGIVHAVYIIAKR 43 S. epidermidis C. jeikeium C. xerosis C.striatum P. aeruginosa 1T-35 P. aeruginosaEICLTLVFPIRGSYSEAAKFPVPIHIVEDG 44 TVELPK 1T-36 S. aureusVYRHLRFIDGKLVEIRLERK 45 S. epidermidis C. jeikeium C. xerosis C.striatum P. aeruginosa 1T-37 S. mutans YIVGALVILAVAGLIYSMLRKA 46 S.aereus S. epidermidis C. jeikeium C. xerosis C. striatum P. aeruginosa1T-38 S. mutans VMFVLTRGRSPRPMIPAY 47 S. aereus S. epidermidis C.jeikeium C. xerosis C. striatum P. aeruginosa 1T-39 S. mutansFGFCVWMYQLLAGPPGPPA 48 P. aeruginosa 1T-40 S. mutans QRVSLWSEVEHEFR 49P. aeruginosa 1T-41 S. mutans KRGSKIVIAIAVVLIVLAGVWVW 50 S. aureus S.epidermidis C. jeikeium C. striatum P. aeruginosa 1T-42 S. aureusTVLDWLSLALATGLFVYLLVALLRADRA 51 S. epidermidis C. xerosis C. striatum P.aeruginosa 1T-43 C. jeikium DRCLSVLSWSPPKVSPLI 52 P. aeruginosa 1T-44 S.mutans DPALADFAAGMRAQVRT 53 S. aureus S. epidermidis C. jeikeium C.striatum P. aeruginosa 1T-45 S. aureus WTKPSFTDLRLGFEVTLYFANR 54 S.epidermidis C. striatum P. aeruginosa 1T-46 S. aureus FSFKQRVMFRKEVERLR55 S. epidermidis C. jeikeium C. xerosis C. striatum P. aeruginosa 1T-47S. mutans VIKISVPGQVQMLIP 56 S. epidermidis P. aeruginosa 1T-48 S.aureus KLQVHHGRATHTLLLQPPLCAPGTIR 57 S. epidermidis C. jeikeium C.xerosis C. striatum P. aeruginosa 1T-49 S. aureusSLVRIHDQQPWVTRGAFIDAARTCS 58 S. epidermidis C. jeikeium P. aeruginosa1T-50 P. aeruginosa HSDEPIPNILFKSDSVH 59 1T-51 S. aureusGKPKRMPAEFIDGYGQALLAGA 60 P. aeruginosa 1T-52 S. aureusDEYPAKLPLSDKGATEPRRH 61 C. xerosis P. aeruginosa 1T-53 P. aeruginosaSDILAEMFEKGELQTLVKDAAAKANA 62 1T-54 S. epidermidis RWVSCNPSWRIQ 63 C.xerosis C. striatum P. aeruginosa 1T-55 C. xerosisNHKTLKEWKAKWGPEAVESWATLLG 64 P. aeruginosa 1T-56 C. xerosisLALIGAGIWMIRKG 65 P. aeruginosa 1T-57 P. aeruginosaRLEYRRLETQVEENPESGRRPMRG 66 1T-58 P. aeruginosa CDDLHALERAGKLDALLSA 671T-59 S. aureus AVGNNLGKDNDSGHRGKKHRKHKHR 68 S. epidermidis P.aeruginosa 1T-60 S. aureus YLTSLGLDAAEQAQGLLTILKG 69 S. epidermidis C.jeikeium C. striatum P. aeruginosa 1T-61 P. aeruginosaHATLLPAVREAISRQLLPALVPRG 70 1T-62 S. epidermidis GCKGCAQRDPCAEPEPYFRLR71 P. aeruginosa 1T-63 S. aureus EPLILKELVRNLFLFCYARALR 72 S.epidermidis C. jeikeium C. xerosis C. striatum P. aeruginosa 1T-64 S.aureus QTVHHIHMHVLGQRQMHWPPG 73 S. epidermidis C. jeikeium C. xerosis C.striatum P. aeruginosa 1T-65 S. mutans HARAAVGVAELPRGAAVEVELIAAVRP 74 S.aureus S. epidermidis C. jeikeium C. xerosis C. striatum P. aeruginosa1T-66 S. mutans DTDCLSRAYAQRIDELDKQYAGIDKPL 75 S. aureus S. epidermidisC. jeikeium C. xerosis C. striatum P. aeruginosa 1T-67 S. aureusGQRQRLTCGRVSGCSEGPSREAAR 76 S. epidermidis C. jeikeium C. xerosis C.striatum P. aeruginosa 1T-68 S. mutans GGTKEIVYQRG 77 S. aureus C.jeikeium C. xerosis C. striatum P. aeruginosa 1T-69 S. mutansILSQEADRKKLF 78 P. aeruginosa 1T-70 S. aureus NRQAQGERAHGEQQG 79 C.jeikeium P. aeruginosa 1T-71 P. aeruginosa KIDTNQWPPNKEG 80 1T-72 P.aeruginosa EPTDGVACKER 81 1T-73 S. pneumoniaeGWWEELLHETILSKFKITKALELPIQL 82 1T-74 S. pneumoniaeDIDWGRKISCAAGVAYGAIDGCATTV 83 1T-75 S. pneumoniaeGVARGLQLGIKTRTQWGAATGAA 84 1T-76 S. pneumoniae EMRLSKFFRDFILWRKK 851T-77 S. pneumoniae EMRISRIILDFLFLRKK 86 1T-78 S. pneumoniaeFFKTIFVLILGALGVAAGLYIEKNYIDK 87 1T-79 S. pneumoniaeFGTPWSITNFWKKNFNDRPDFDSDRRRY 88 1T-80 S. pneumoniae GGNLGPGFGVIIP 891T-81 S. pneumoniae AIATGLDIVDGKFDGYLWA 90 1T-82 S. pneumoniaeFGVGVGIALFMAGYAIGKDLRKKFGKSC 91 1T-83 S. pneumoniaeQKPRKNETFIGYIQRYDIDGNGYQSLPC 92 PQN 1T-84 S. pneumoniaeFRKKRYGLSILLWLNAFTNLVNSIHAFY 93 MTLF 1T-85 A. naeslundiiVMASLTWRMRAASASLPTHSRTDA 94 F. nucleatum P. gingivalis S. epidermidis S.gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-86S. mitis HRKNPVLGVGRRHRAHNVA 95 S. oralis S. salivarious 1T-87 S. mitisEAVGQDLVDAHHP 96 S. mutans S. oralis 1T-89 S. mitisHEDDKRRGMSVEVLGFEVVQHEE 97 S. mutans 1T-90 S. gordonii RNVIGQVL 98 S.mitis S. mutans S. oralis S. sanguinis 1T-91 S. mitisTSVRPGAAGAAVPAGAAGAAGAGWR 99 S. mutans WP S. oralis S. sanguinis 1T-92S. mitis GQDEGQRRAGVGEGQGVDG 100 S. mutans 1T-93 S. epidermidis AMRSVNQA101 S. gordonii S. mitis S. mutans S. oralis S. sanguinis 1T-94 S. mitisDQVAHSGDMLVQARRRDS 102 S. mutans S. oralis 1T-95 S. gordoniiGHLLRVGGRVGGVGGVAGACAQPFGGQ 103 S. mitis S. mutans S. oralis S.sanguinis 1T-96 S. gordonii VAGACAQPFGGQ 104 S. mitis S. mutans S.oralis S. sanguinis 1T-97 A. naeslundii GVAERNLDRITVAVAIIWTITIVGLGLV 105F. nucleatum AKLG P. gingivalis S. epidermidis S. gordonii S. mitis S.mutans S. oralis S. salivarious S. sanguinis 1T-98 A. naeslundiiVRSAKAVKALTAAGYTGELVNVSGGM 106 F. nucleatum KAWLGQ P. gingivalis S.epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S.sanguinis 1T-99 S. gordonii MKAWLGQ 107 S. mitis S. mutans S. oralis S.sanguinis 1T-100 S. gordonii LDPLEPRIAPPGDRSHQGAPACHRDPLR 108 S. mitisGRSARDAER S. mutans 1T-101 A. naeslundii RLRVGRATDLPLTSFAVGVVRNLPDAP 109P. gingivalis AH S. epidermidis S. gordonii S. mitis S. mutans S. oralisS. sanguinis 1T-102 A. naeslundii WKRLWPARILAGHSRRRMRWMVVWR 110 F.nucleatum YFAAT P. gingivalis S. epidermidis S. gordonii S. mitis S.mutans S. oralis S. salivarious S. sanguinis 1T-103 A. naeslundiiAQFYEAIITGYALGAGQRIGQL 111 F. nucleatum P. gingivalis S. epidermidis S.gordonii S. mitis S. mutans S. oralis S. sanguinis 1T-104 S. mitisRAVAAHLQGRHHGHQVRRQRHGQR 112 1T-105 S. epidermidis GEGLPPPVLHLPPPRMSGR113 S. gordonii S. mitis S. mutans S. oralis 1T-106 S. gordoniiDALRRSRSQGRRHR 114 S. mitis S. mutans S. oralis S. salivarious 1T-107 A.naeslundii SPVPRFTAVGGVSRGSP 115 S. epidermidis S. gordonii S. mitis S.mutans S. oralis S. salivarious S. sanguinis 1T-108 S. gordoniiWGPLGPERPLW 116 S. mitis S. mutans S. oralis S. salivarious S. sanguinis1T-109 A. naeslundii VTTNVRQGAGS 117 S. epidermidis S. gordonii S. mitisS. mutans S. oralis S. salivarious S. sanguinis 1T-110 A. naeslundiiLAAKTAVCVGRAFM 118 P. gingivalis S. epidermidis S. gordonii S. mitis S.mutans S. oralis S. sanguinis 1T-111 A. naeslundiiGRLSRREEDPATSIILLRGAYRMAVF 119 F. nucleatum P. gingivalis S. epidermidisS. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis1T-112 S. gordonii SDNDGKLILGTSQ 120 1T-113 S. mitisHGAHQRTGQRLHHHRGRTVSGCRQNP 121 VAGVDPDEHR 1T-114 A. naeslundiiRQAPGPGLVTITAACSAPGSRSR 122 P. gingivalis S. epidermidis S. gordonii S.mitis S. mutans S. oralis S. sanguinis 1T-115 A. naeslundii LLIERFSNHH123 F. nucleatum P. gingivalis S. epidermidis S. gordonii S. mitis S.mutans S. oralis S. salivarious S. sanguinis 1T-116 A. naeslundiiMILHRRRDR 124 P. gingivalis S. epidermidis S. gordonii S. mitis S.mutans S. oralis S. salivarious S. sanguinis 1T-117 S. mutansGPGVVGPAPFSRLPAHALNL 125 1T-118 A. naeslundiiTASPPAPSDQGLRTAFPATLLIALAALA 126 F. nucleatum RISR P. gingivalis S.epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S.sanguinis 1T-119 S. gordonii SPATQKAPTRAQPSRAPVQDCGDGRPT 127 S. mitisAAPDDVERLSPR S. mutans S. oralis 1T-120 A. naeslundiiDVRDRVDLAGADLCAAHATR 128 F. nucleatum P. gingivalis S. epidermidis S.gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-121S. gordonii FAKETGFGIGGAQEGWWIIADIYGPNPF 129 S. mitis S. mutans S.oralis S. salivarious S. sanguinis 1T-122 S. mitisGAIPDPVTHRVDWEEDHQTRPSR 130 1T-123 S. gordoniiLVRRNAVAGRSDGLAGAEQLDLVRLQ 131 GVL 1T-124 S. mitis LFDERNKIA 132 S.mutans S. oralis 1T-125 S. epidermidis DAITGGNPPLSDTDGLRP 133 S.gordonii S. mutans S. oralis 1T-126 S. gordonii QGLARPVLRRIPL 134 S.mitis S. mutans 1T-127 A. naeslundii YDPVPKRKNKNSEGKREE 135 F. nucleatumP. gingivalis T. denticola S. gordonii S. mitis S. mutans S. oralis S.salivarious S. sanguinis 1T-128 A. naeslundii SGSAIRMLEIATKMLKR 136 P.gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S.salivarious S. sanguinis 1T-129 A. naeslundii YDKYIKYLSIQPPFIVYFI 137 P.gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S.salivarious S. sanguinis 1T-130 A. naeslundiiQKIIDMSKFLFSLILFIMIVVIYIGKSIGG 138 F. nucleatumYSAIVSSIMLELDTVLYNKKIFFIYK P. gingivalis S. epidermidis S. gordonii S.mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-131 A.naeslundii DEVWKMLGI 139 F. nucleatum P. gingivalis T. denticola S.gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-132A. naeslundii YSKKLFEYFYFIIFILIRYLIFYKIIQNKNY 140 F. nucleatum YINNIAYNP. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S.salivarious S. sanguinis 1T-133 A. naeslundiiYFIKDDNEALSKDWEVIGNDLKGTIDK 141 P. gingivalis YGKEFKVR S. epidermidis S.gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-134A. naeslundii SRLVREIKKKCRKS 142 F. nucleatum P. gingivalis S.epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S.sanguinis 1T-135 A. naeslundii FESLLPQATKKIVNNKGSKINKIF 143 P.gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S.salivarious S. sanguinis 1T-136 A. naeslundii ELLTQIRLALLYSVNEW 144 F.nucleatum P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S.oralis S. salivarious S. sanguinis 1T-137 A. naeslundiiPLNFYRAVKENRLPLSEKNINDFTNIKL 145 F. nucleatumKVSPKLINLLQESSIFYNFSPKKRNTN P. gingivalis S. epidermidis S. gordonii S.mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-138 A.naeslundii YPNEYCIFLENLSLEELKEIKAINGETLN 146 F. nucleatum LEEIINERKNLKDP. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S.salivarious S. sanguinis 1T-139 A. naeslundii AVAGAAVGALLGNDARSTAVGAAIGG147 S. gordonii ALGAGAGELTKNK S. mitis S. mutans S. oralis 1T-140 A.naeslundii IKGTIAFVGEDYVEIRVDKGVKLTFRKS 148 F. nucleatum AIANVINNNQQ P.gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S.salivarious S. sanguinis 1T-141 F. nucleatumKKFIILLFILVQGLIFSATKTLSDIIAL 149 P. gingivalis S. epidermidis S.gordonii S. mitis S. mutans S. oralis S. sanguinis 1T-142 A. naeslundiiFTQGIKRIVLKRLKED 150 F. nucleatum P. gingivalis T. denticola S. gordoniiS. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-143 A.naeslundii MPKRHYYKLEAKALQFGLPFAYSPIQL 151 F. nucleatum LK P. gingivalisS. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivariousS. sanguinis 1T-144 A. naeslundii IIELHPKSWTQDWRCSFL 152 F. nucleatum P.gingivalis T. denticola S. gordonii S. mitis S. mutans S. oralis S.salivarious S. sanguinis 1T-145 S. mitis VEAGKRNISLENIEKISKGLGISISELFKY153 S. mutans IEEGEDKIG S. oralis 1T-146 A. naeslundiiRNSADNQTKIDKIRIDISLWDEHLNIVK 154 F. nucleatum QGK P. gingivalis T.denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S.sanguinis 1T-147 A. naeslundii GVENRRFYERDVSKVSMMTSEAVAPR 155 F.nucleatum GGSK P. gingivalis T. denticola S. gordonii S. mitis S. mutansS. oralis S. salivarious S. sanguinis 1T-148 A. naeslundiiIVELDDTTILERALSMLGEANA 156 F. nucleatum P. gingivalis T. denticola S.gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-149A. naeslundii SVRAVKPIDETVARHFPGDFIVN 157 F. nucleatum P. gingivalis T.denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S.sanguinis 1T-150 A. naeslundii YINRRLKKAFSDADIKEAPAEFYEELRR 158 F.nucleatum VQYV P. gingivalis T. denticola S. gordonii S. mitis S. mutansS. oralis S. salivarious S. sanguinis 1T-151 A. naeslundiiSVRAVKPIDEIVAWHFPGDFIVN 159 F. nucleatum P. gingivalis T. denticola S.gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-152A. naeslundii YVSADESAYNHIVTDDIPLADRRIEAVQQ 160 F. nucleatum P.gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S.salivarious S. sanguinis 1T-153 A. naeslundii YIACPGYFY 161 F. nucleatumP. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S.salivarious S. sanguinis 1T-154 P. gingivalis YFSFLEIVGMARR 162 1T-155A. naeslundii LKLAFGVYPFQAMSQSDTAVSERNVL 163 F. nucleatum WR P.gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S.salivarious S. sanguinis 1T-156 A. naeslundiiGRFQISIRGEEKSKVKVQGKGTFTDRNTT 164 F. nucleatum P. gingivalis T.denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S.sanguinis 1T-157 A. naeslundii RRFRKTTENREKSKNKKAVLGLSTTST 165 F.nucleatum ASY P. gingivalis T. denticola S. gordonii S. mitis S. mutansS. oralis S. salivarious S. sanguinis 1T-158 A. naeslundiiWENKPSPLGSIKKLQGLVYRLIGYRHF 166 F. nucleatum WV P. gingivalis S.epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S.sanguinis 1T-159 P. gingivalis IFSLHHFALICSEMGTFAVSKRAKYKWE 167 VL1T-160 A. naeslundii AQYKYINKLLN 168 F. nucleatum P. gingivalis T.denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S.sanguinis 1T-161 A. naeslundii NKVLQVEVMWDGSVVGRPAGVISIKSS 169 F.nucleatum KKG P. gingivalis S. epidermidis S. gordonii S. mitis S.mutans S. oralis S. salivarious S. sanguinis 1T-162 A. naeslundiiQKAKEESDRKAAVSYNGFHRVNVVSIPK 170 F. nucleatum P. gingivalis T. denticolaS. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis1T-163 A. naeslundii MENILIYIPMVLSPFGSGILLFLGKDRRY 171 F. nucleatum MLP. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S.salivarious S. sanguinis 1T-164 A. naeslundiiKKSHSQGKRKLKDLNSAYKIDNQLHYA 172 F. nucleatum LR P. gingivalis S.epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S.sanguinis 1T-165 A. naeslundii CYDSFDFSIFVTFANRMKLSVGS 173 F. nucleatumP. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S.salivarious S. sanguinis 1T-166 A. naeslundii AQSAGQIKRKSKVRIHV 174 F.nucleatum P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S.oralis S. salivarious S. sanguinis 1T-167 A. naeslundiiSRMSEHSPAGLVFEVGPMDKGSFIILDS 175 F. nucleatum YHPTVKK P. gingivalis S.epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S.sanguinis 1T-168 A. naeslundii ELHRIMSTEKIGAVTKMNFDTAPIMSILP 176 F.nucleatum IDIYPKEVGIGS P. gingivalis S. epidermidis S. gordonii S. mitisS. mutans S. oralis S. salivarious S. sanguinis 1T-169 A. naeslundiiFARVRRLHQNRILTQPLTNLKYCLRQPI 177 F. nucleatum YSD P. gingivalis S.epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S.sanguinis 1T-170 P. gingivalis AYGKVFSMDIMLSENDKLIVLRISHHSA 178 WH1T-171 A. naeslundii SVRAVKPIDKTVARHFPGDFIVN 179 F. nucleatum P.gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S.salivarious S. sanguinis 1T-172 A. naeslundii FEGLKNLLGDDII 180 F.nucleatum P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S.oralis S. salivarious S. sanguinis 1T-173 A. naeslundii LFRKEDQEHVLL 181F. nucleatum P. gingivalis S. gordonii S. mitis S. mutans S. oralis S.salivarious S. sanguinis 1T-174 A. naeslundii SGGSDTDGSSSGEPGSHSGDL 182F. nucleatum P. gingivalis T. denticola S. gordonii S. mitis S. mutansS. oralis S. salivarious S. sanguinis 1T-175 A. naeslundii GEPGSHSGDL183 F. nucleatum P. gingivalis S. epidermidis S. gordonii S. mitis S.mutans S. oralis S. salivarious S. sanguinis 1T-176 A. naeslundiiPVGDIMSGFLRGANQPRFLLDHISFGS 184 P. gingivalis S. epidermidis S. gordoniiS. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-177 P.gingivalis GTNVPTQILGYSREERFDYEPAPEQR 185 S. gordonii S. mitis S. mutansS. oralis S. salivarious S. sanguinis 1T-178 A. naeslundiiLLASHPERLSLGVFFVYRVLHLLLENT 186 F. nucleatum P. gingivalis S.epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S.sanguinis 1T-179 A. naeslundii TCYPLIQRKTDRAYEA 187 F. nucleatum P.gingivalis T. denticola S. gordonii S. mitis S. mutans S. oralis S.salivarious S. sanguinis 1T-180 A. naeslundii VVFGGGDRLV 188 F.nucleatum P. gingivalis T. denticola S. gordonii S. mitis S. mutans S.oralis S. salivarious S. sanguinis 1T-181 A. naeslundii YGKESDP 189 F.nucleatum P. gingivalis T. denticola S. gordonii S. mitis S. mutans S.oralis S. salivarious S. sanguinis 1T-182 A. naeslundiiLTASICRQWNDNSTPYQR 190 F. nucleatum P. gingivalis T. denticola S.gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-183A. naeslundii PLRSFVAEKAEHAFRVVRIADFDFGHS 191 F. nucleatum P. gingivalisS. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivariousS. sanguinis 1T-184 A. naeslundii ALLVLNLLLMQFFFGKNM 192 F. nucleatum P.gingivalis T. denticola S. gordonii S. mitis S. mutans S. oralis S.salivarious S. sanguinis 1T-185 A. naeslundii HYHFLLEFGFHKGDYLE 193 F.nucleatum P. gingivalis T. denticola S. gordonii S. mitis S. mutans S.oralis S. salivarious S. sanguinis 1T-188 S. sanguinis HRKDVYKK 1941T-190 A. naeslundii IQIIVNAFVEKDKTGAVIEVLYASNNHE 195 F. nucleatumKVKAKYEELVAIS P. gingivalis S. epidermidis S. gordonii S. mitis S.mutans S. oralis S. salivarious S. sanguinis 1T-192 S. sanguinisILVLLALQVELDSKFQY 196 1T-193 S. sanguinis LMIFDKHANLKYKYGNRSFGVEAIM 1971T-195 S. mutans AASGFTYCASNGVWHPY 198 1T-196 F. nucleatumKPEKEKLDTNTLMKVVNKALSLFDRLL 199 S. sanguinis IKFGA 1T-197 A. naeslundiiTEILNFLITVCADRENWKIKHGLSDSVL 200 F. nucleatum LIFFARFTGAEYW P.gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S.salivarious S. sanguinis 1T-198 P. gingivalisMPVSKKRYMLSSAYATALGICYGQVAT 201 S. epidermidis DEKESEITAIPDLLDYLSVEEYLLS. gordonii S. mitis S. mutans S. oralis S. sanguinis 1T-199 S.sanguinis RAGRIKKLSQKEAEPFEN 202 1T-200 A. naeslundiiMRFKRFDRDYALSGDNVFEVLTASCDV 203 F. nucleatum IERNLSYREMCGLMQ S.epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S.sanguinis 1T-201 S. sanguinis KRKHENVIVAEEMRVIKN 204 1T-202 A.naeslundii LCRLEKLCKQFLRQDKVVTYYLMLPYK 205 F. nucleatum RAIEAFYQELKERSP. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S.salivarious S. sanguinis 1T-203 A. naeslundiiYPFCLATVDHLPEGLSVTDYERVQRLV 206 F. nucleatum SQFLLNKEER P. gingivalis S.epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S.sanguinis 1T-207 F. nucleatum SPLEKYGTGSMTALTFLLGCCLLVLSKK 207 S.sanguinis SR 1T-208 Unanalyzed KRKRWAILTLFLAGLGAVGIVLATF 208 1T-215 S.sanguinis VCFKDISVFLSPFRGQEVLFCGKAKHSL 209 IYVIGT 1T-216 S. sanguinisFFLNVIAIRIPHF 210 1T-217 F. nucleatum MLSNVLSRSVVSPNVDIPNSMVILSPLLI 211S. sanguinis SISNYH 1T-218 F. nucleatum KLIFAALGLVFLLIGLRDSRSK 212 S.sanguinis 1T-219 S. sanguinis RNINVSATFITEKSLV 213 1T-221 A. naeslundiiDIGRIIGKKGRTITAIRSIVYSVPTQGKK 214 F. nucleatum VRLVIDEK P. gingivalis S.epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S.sanguinis 1T-222 F. nucleatum RIEASLISAIMFSMFNAIVKFLQK 215 S. sanguinis1T-223 A. naeslundii NQKMEINSMTSEKEKMLAGHFHNEAN 216 F. nucleatumFAVIFKYSLFYNFF P. gingivalis S. epidermidis S. gordonii S. mitis S.mutans S. oralis S. salivarious S. sanguinis 1T-225 A. naeslundiiRRSLGNSASFAEWIEYIRYLHYIIRVQFI 217 F. nucleatum HFFSKNKKI P. gingivalisS. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivariousS. sanguinis 1T-226 A. naeslundii KLQEKQIDRNFERVSGYSTYRAVQAAK 218 F.nucleatum AKEKGFISLEN S. epidermidis S. gordonii S. mitis S. mutans S.oralis S. salivarious S. sanguinis 1T-228 A. naeslundiiIFKLFEEHLLYLLDAFYYSKIFRRLKQGL 219 F. nucleatum YRRKEQPYTQDLFRM P.gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S.salivarious S. sanguinis 1T-230 A. naeslundiiEFLEKFKVLKQPRKANNISKNRVAMIFL 220 F. nucleatum TIHKSRGFLSSPY P.gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S.salivarious S. sanguinis 1T-233 A. naeslundiiTDQELEHLIVTELESKRLDFTYSKDITEF 221 P. gingivalis FDEAFPEYDQNY S.epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S.sanguinis 1T-234 A. naeslundii DNFYLILKMEERGKSKKTSQTRGFRAFF 222 F.nucleatum DIIRKKIKKEDGK P. gingivalis S. epidermidis S. gordonii S.mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-237 S.sanguinis EDPVPNHFTLRRNKKEKPSKS 223 1T-238 A. naeslundiiIFNRRKFFQYFGLSKEAMVEHIQPFILDI 224 F. nucleatum WQIHLF P. gingivalis S.epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S.sanguinis 1T-239 A. naeslundii ADDLLNKRLTDLIMENAETVKTIDLDN 225 S.gordonii SD S. mitis S. mutans S. oralis S. sanguinis 1T-240 A.naeslundii VILGNGISNIAQTLGQLPNIAWVWIYMV 226 F. nucleatum LIAALLEESNVC P.gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S.salivarious S. sanguinis 1T-242 F. nucleatumKQVQNTTLIICGTVLLGILFKSYLKSQKSV 227 S. sanguinis 1T-243 A. naeslundiiSENIARFAAAFENEQVVSYARWFRRSW 228 P. gingivalis RGSGSSSRF S. epidermidisS. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis1T-248 S. sanguinis IGGALNSCG 229 1T-249 F. nucleatumVFSVLKHTTWPTRKQSWHDFISILEYSA 230 S. sanguinis FFALVIFIFDKLLTLGLAELLKRF1T-250 S. mitis LVQGDTILIENHVGTPVKDDGKDCLIIR 231 S. mutans EADVLAVVND S.oralis 1T-252 F. nucleatum MKKNLKRFYALVLGFIIGCLFVSILIFIGY 232 S.sanguinis 1T-253 A. naeslundii KTKESLTQQEKKFLKDYDRKSLHHFRD 233 F.nucleatum ILTYCFILDKLTNK P. gingivalis S. epidermidis S. gordonii S.mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-256 S.sanguinis KGKSLMPLLKQINQWGKLYL 234 1T-257 A. naeslundiiIILAKAADLAEIERIISEDPFKINEIANYDI 235 F. nucleatum IEFCPTKSSKAFEKVLK P.gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S.salivarious S. sanguinis 1T-258 A. naeslundiiTINIDDKVLDYLKKINSKAITIDLIGCAS 236 F. nucleatum P. gingivalis T.denticola S. mitis S. mutans S. oralis 1T-259 F. nucleatumEKLKKILLKLAVCGKAWYTL 237 P. gingivalis T. denticola S. mitis S. mutansS. oralis S. sanguinis 1T-260 A. naeslundii NILYFIHDENQWEPQKAEIFRGSIKHCA238 P. gingivalis WLSS S. epidermidis S. gordonii S. mitis S. mutans S.oralis S. sanguinis 1T-261 F. nucleatum SFEKNKIENNLKIAQAYIYIKPKPRICQA239 S. mutans S. oralis S. sanguinis 1T-262 A. naeslundii LSLPLIVLTKSI240 F. nucleatum P. gingivalis S. epidermidis S. gordonii S. mitis S.mutans S. oralis S. salivarious S. sanguinis 1T-263 A. naeslundiiFIAVSFTGNPATFKLVIGCKADN 241 F. nucleatum P. gingivalis S. epidermidis S.gordonii S. mitis S. oralis S. salivarious S. sanguinis 1T-264 S.sanguinis LEGKFYMAEDFDKTPECFKDYV 242 1T-265 A. naeslundiiGMFENLLMINFQIMNDLKIEIVVKDRIC 243 F. nucleatum AV P. gingivalis S.epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S.sanguinis 1T-266 S. sanguinis RAGTWLVVDEIR 244 1T-267 A. naeslundiiRIKEERKNRSYKFFIWRLFDEKTGFI 245 F. nucleatum P. gingivalis T. denticolaS. mitis S. mutans S. oralis S. sanguinis 1T-268 F. nucleatumPITPKKEKCGLGTYAPKNPVFSKSRV 246 S. mutans S. oralis S. sanguinis 1T-269F. nucleatum PLYVAAVEKINTAKKH 247 S. mutans S. oralis S. sanguinis1T-270 F. nucleatum VHEFDIQKILQNR 248 S. mutans S. oralis S. sanguinis1T-271 A. naeslundii FLIQKFLLIKTFPPYRKKYVVIVSQTGTA 249 F. nucleatum P.gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S.salivarious S. sanguinis 1T-272 F. nucleatumQLAPIDKQLKAVKKIAFYESESTAAKAV 250 S. mutans TVA S. oralis S. sanguinis1T-273 F. nucleatum YNEPNYKWLESYKIYKQRCEDRTGMY 251 P. gingivalis YTEETT. denticola S. mitis S. mutans S. oralis 1T-274 F. nucleatumETTTEINAIKLHRIKQRSPQGTRRVN 252 S. mutans S. oralis S. sanguinis 1T-275A. naeslundii QVLKNFSISRRYKINNPFFKILLFIQLRTL 253 F. nucleatum P.gingivalis T. denticola S. epidermidis S. gordonii S. mitis S. mutans S.oralis S. salivarious S. sanguinis 1T-276 A. naeslundiiILTLLILGSIGFFILKIKLKLGRF 254 F. nucleatum P. gingivalis S. epidermidisS. gordonii S. mitis S. mutans S. oralis S. sanguinis 1T-277 A.naeslundii IYYMRFVNKPLEKTFFKI 255 F. nucleatum P. gingivalis T.denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S.sanguinis 1T-278 A. naeslundii SINSSAGIQPHCLSSSFVLRTKHCFY 256 F.nucleatum P. gingivalis S. gordonii S. mitis S. mutans S. oralis S.salivarious S. sanguinis 1T-279 A. naeslundii FVLRTKHCFY 257 F.nucleatum P. gingivalis S. gordonii S. mitis S. mutans S. oralis S.salivarious S. sanguinis 1T-280 A. naeslundiiTNNKNKVIIKAIKFKNKDFINLDLFIYRR 258 F. nucleatum P. gingivalis T.denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S.sanguinis 1T-281 A. naeslundii KYEKLTKENLFIRNSGNMCVFIYFLFFG 259 F.nucleatum P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S.oralis S. salivarious S. sanguinis 1T-282 F. nucleatum ISLVFPAYT 260 P.gingivalis S. gordonii S. mitis S. mutans S. oralis S. salivarious S.sanguinis 1T-283 A. naeslundii LCTKLEDKQRGRIPAELFIISPIKILERND 261 F.nucleatum AL P. gingivalis T. denticola S. epidermidis S. gordonii S.mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-284 A.naeslundii FQYYFSLKRV 262 F. nucleatum P. gingivalis S. gordonii S.mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-285 A.naeslundii FFPYYLADFYKQLKFLNEYQTKNKDKV 263 F. nucleatum VEFK P.gingivalis S. gordonii S. mitis S. mutans S. oralis S. salivarious S.sanguinis 1T-286 S. sanguinis LGFFNNKADLVKADTERDNRMSSLKIK 264 DL 1T-287P. gingivalis KGYPLPFQYRLNNH 265 T. denticola S. gordonii S. mitis S.mutans S. oralis S. salivarious S. sanguinis 1T-288 F. nucleatumRWVGGEPSADIYLSAKDTKT 266 S. gordonii S. salivarious S. sanguinis 1T-289F. nucleatum EPSADIYLSAKDTKT 267 P. gingivalis S. gordonii S. mitis S.mutans S. oralis S. sanguinis 1T-290 A. naeslundii IINQLNLILLRLMEILIL268 F. nucleatum P. gingivalis S. gordonii S. mitis S. mutans S. oralisS. salivarious S. sanguinis 1T-291 A. naeslundiiDMKIIKLYIKILSFLFIKYCNKKLNSVKL 269 F. nucleatum KA P. gingivalis T.denticola S. mitis S. mutans S. oralis 1T-292 A. naeslundiiIINQLNLILLRLMEILIL 270 F. nucleatum P. gingivalis S. epidermidis S.gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-293A. naeslundii HVEDCFLLSNARTTAIHGRANPARGEPR 271 F. nucleatum TRSE P.gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S.salivarious S. sanguinis 1T-294 T. denticola YDKIADGVFKIGKRGVL 2721T-295 S. mitis KYKLKKIIL 273 S. salivarious S. sanguinis 1T-296 A.naeslundii EYSQQSFKAKPCSERGVLSP 274 F. nucleatum P. gingivalis S.gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-297A. naeslundii RSLRLNNALTKLPKLWYNRIKEAFYAY 275 F. nucleatum NDYDK T.denticola S. mitis S. mutans S. oralis 1T-298 A. naeslundiiILNKKPKLPLWKLGKNYFRRFYVLPTFLA 276 F. nucleatum P. gingivalis T.denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S.sanguinis 1T-299 A. naeslundii SMLTSFLRSKNTRSLKMYKDVHF 277 F. nucleatumS. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivariousS. sanguinis 1T-300 A. naeslundii PLIISKAQIKMSGDILGSCFKLFYLRPFF 278 F.nucleatum P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S.oralis S. salivarious S. sanguinis 1T-301 F. nucleatum SKLPRVLDASLKL 279S. gordonii S. sanguinis 1T-302 A. naeslundii IIIILPKIYLVCKTV 280 P.gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S.salivarious S. sanguinis 1T-303 A. naeslundii LDYENMDCKKRIRI 281 F.nucleatum P. gingivalis S. gordonii S. mitis S. mutans S. oralis S.salivarious S. sanguinis 1T-304 P. gingivalis STAGEASRRTASEASRRTAAKLRG282 TT-305 F. nucleatum ARNALNMRDVPVDAAIIGIIDGMDEE 283 TT-306 F.nucleatum KILNEAEGKLLKVIEKNGEIDIEEI 284 TT-307 F. nucleatumNGDKKAKEELDKWDEVIKELNIQF 285 TT-308 F. nucleatumGLVIIPNLIALIILFSQVRQQTKDYFSNPK 286 LSSR TT-309 F. nucleatumEPLPLTKYDKKDTEMKKVFKEILAGKV 287 GYEKEEE TT-310 F. nucleatumTKLKKNNKLLSAKKENTLHTKDK 288 TT-311 S. mutans AIFDAMHNL 289 S. sobrinusPVCFBP2461 P. fluorescens DLys-Dorn-Gly-DThr-Thr-Gln-Gly-DSer- 290 cDOrnCHA0 P. fluorescens Asp-DOrn-Lys-c(Thr-Ala-Ala-DOrn-Lys) 291 CFBP2461 P.putida Asp-Lys-DAsp-Ser-DThr-DAla-Thr-DLys- 292 cOrn NCPPB2192 P.tolaasii DSer-Lys-Ser-DSer-Thr-DSer-Orn-Thr- 293 DSer-cDOrn PyC-E P.aeruginosa DSer-Arg-DSer-Orn-c(Lys-Orn-Thr-Thr) 294 PyR P. aeruginosaDSer-Dab-Orn-DGln-Gln-DOrn-Gly 295 PyPaTII P. aeruginosaDSer-DOrn-Orn-Gly-DThr-Ser-cOrn 296 Py Pap P. aptataDAla-Lys-Thr-DSer-Orm-cOrn 297 Py Pau P. aureofaciensDSer-DOrn-Gly-DThr-Thr-Gln-Gly-DSer- 298 cDOrn Ps P. fluorescensLys-DAsp-Ala-DThr-Ala-cDOrn 299 Py I-III P. fluorescensAsn-DOrn-Lys-c(Thr-DAla-DAla-DOrn- 300 Lys) Py Gm P. fluorescensDAla-Lys-Gly-Gly-Asp-DGln-DSer-Ala- 301 DAla-DAla-Ala-cOrn Py Pf 12 P.fluorescens DSer-Lys-Gly-Orn-DSer-Ser-Gly-c(Lys- 302 DOrn-Glu-Ser) Py PfP. fluorescens c(DSer-Dab)-Gly-Ser-Asp-Ala-Gly-DAla- 303 2798 Gly-cOrnPy Pf P. fluorescens Ser-Lys-Gly-Orn-c(Lys-DOrn-Ser) 304 13525 Py Pf P.fluorescens DAla-DLys-Gly-Gly-Asp-DGln-Dab-Ser- 305 17400 DAla-cOrn Py51W P. fluorescens DAla-DLys-Gly-Gly-DAsp-DGln-DSer-Ala- 306Gly-DThr-cOrn Py 9AW P. fluorescens DSer-Lys-His-DThr-Ser-cOrn 307 PsA225 P. fluorescens DSer-DAla-DOrn-Gly-c(DSer-DAsp-DSer- 308 DThr) Py Pf1.3 P. fluorescens DAla-DLys-Gly-Gly-Asp-c(DGln-Dab)-Gly- 309 Ser-cOrnPy Pf P. fluorescens DSer-Lys-Gly-Orn-Ser-DSer-Gly-c(Lys- 310 18.1DOrn-Ser) Py Pf P. fluorescens DSer-DOrn-Ala-Gly-DThr-Ala-cOrn 311 PL7Py Pf P. fluorescens DLys-DOrn-Ala-Gly-DThr-Ser-cOrn 312 PL8 Py Pf P.fluorescens DSer-DSer-Orn-DSer-DSer-c(DSer-Orn- 313 BTP7 Lys-Lys) Ps589A P. putida Asp-Lys-Asp-DSer-Thr-DAla-DGlu-DSer- 314 cOrn Py Pp 1,2P. putida Ser-Thr-DSer-Orn-Asp-DGln-Dab-Ser- 315 DThr-cOrn Py Pp P.putida Asp-DOrn-DDab-Thr-Gly-DSer-Ser-Asp- 316 C2,3 Thr Py G4R P. putidaAsp-Orn-DAsp-Dab-Gly-Ser-cOrn 317 Py P. putidaAsp-DOrn-DDab-Thr-Gly-DSer-DSer-Thr- 318 PpBTP16 Asp Py P. putidaDSer-DAla-DOrn-Gly-DAla-DAsp-c(DSer- 319 Pp39167 DThr) iPy Pp P. putidaAsp-Ala-Asp-DOrn-Ser-cOrn 320 BTP1 Py P. tolaasiiDSer-Lys-Ser-DSer-Thr-DSer-Orn-Thr- 321 PT2192 DSer-Orn Ps 7SR1Pseudomonas spp. DSer-DAsp-DThr-c(DSer-D-Orn-Ala-Gly- 322 DSer) Ps A214Pseudomonas spp. DSer-DAla-Gly-DSer-DAla-DAsp-DThr- 323 DOrn AzoverdinPseudomonas spp. Hse-DHse-Dab-DOrn-DSer-Orn 324 A. macrocytogenesPF-S024 Corynebacteria SKRGRKRKDRRKKKANHGKRPNS 325 spp. PF-001 S.epidermidis MNNWIIVAQLSVTVINEIIDIMKEKQKG 326 M. luteus GK P. mirabilisE. coli P. aeruginosa C. albicans MRSA E. faecalis C. jeikeium PF-002 S.epidermidis NDDAQ 327 P. mirabilis C. albicans C. jeikeium C. jejuniPF-003 S. epidermidis MNNWIKVAQISVTVINEVIDIMKEKQN 328 M. luteus GGK P.mirabilis C. albicans MRSA C. jeikeium PF-004 S. epidermidisARLSKAIIIAVIVVYHLDVRGLF 329 B. subtilis B. fragilis E. coli P.aeruginosa C. albicans S. pneumoniae E. faecalis C. jeikeium PF-005 S.epidermidis MESIFKIKLMNGICRSENMNMKKKNKG 330 E. coli EKI MRSA S.pneumoniae E. faecalis PF-006 S. epidermidis MGIIAGIIKFIKGLIEKFTGK 331M. luteus E. coli P. aeruginosa MRSA E. faecalis C. jeikeium C. jejuniPF-007 S. epidermidis MGIIAGIIKVIKSLIEQFTGK 332 M. luteus E. coli P.aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-008S. epidermidis MIEIGSIAYLNGGSKKYNHILNQENR 333 M. luteus MRSA C. jejuniPF-009 M. luteus SKKYNHILNQENR 334 P. mirabilis C. albicans PF-010 S.epidermidis MDIDVNKLLQAFVYFKSFEKLRHNNS 335 M. luteus E. coli C. albicansPF-011 M. luteus MFCYYKQHKGDNFSIEEVKNIIADNEM 336 E. coli KVN P.aeruginosa S. pneumoniae C. jeikeium PF-012 S. epidermidisWRGPNTEAGGKSANNIVQVGGAPT 337 M. luteus P. mirabilis E. coli P.aeruginosa MRSA S. pneumoniae C. jeikeium C. jejuni PF-013 M. luteusLIQKGLNQTFIVVIRLNNFIKKS 338 P. mirabilis E. coli P. aeruginosa MRSA S.pneumoniae C. jeikeium C. jejuni PF-014 E. coli HPTDNKHN 339 C. jeikeiumPF-015 E. faecalis SIDKRNLYNLKYYE 340 C. jeikeium PF-016 S. epidermidisRKQYDDLSFNFLY 341 E. faecalis C. jeikeium PF-017 E. coli ESIIE 342PF-018 E. coli YYKTYFKEV 343 C. jeikeium PF-020 S. epidermidisMKIILLLFLIFGFIVVVTLKSEHQLTLFSI 344 M. luteus C. albicans MRSA S.pneumoniae E. faecalis PF-021 S. epidermidis FSLNFSKQKYVTVN 345 M.luteus P. mirabilis E. coli C. albicans E. faecalis C. jeikeium PF-022M. luteus MINELKNKNSGIMNNYVVTKESKL 346 P. mirabilis E. coli P.aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C.jejuni PF-023 M. luteus MTKNTIISLENEKTQINDSENESSDLRKAK 347 C. jeikeiumPF-024 M. luteus DLRKAK 348 C. albicans MRSA E. faecalis C. jeikeiumPF-025 S. epidermidis LLIIFRLWLELKWKNKK 349 M. luteus P. mirabilis E.coli P. aeruginosa MRSA E. faecalis C. jejuni PF-026 S. epidermidisSIHFIN 350 M. luteus P. mirabilis C. albicans MRSA E. faecalis C.jeikeium PF-027 M. luteus HNARKYLEFISQKIDGDKLTKEDSL 351 MRSA E. faecalisC. jejuni PF-028 S. epidermidis ALDCSEQSVILWYETILDKIVGVIK 352 M. luteusMRSA PF-029 S. epidermidis NSTNE 353 M. luteus C. albicans C. jejuniPF-030 S. epidermidis MTCHQAPTTTHQSNMA 354 M. luteus P. mirabilis E.coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C.jeikeium C. jejuni PF-031 M. luteus MPHHSTTSSRIVVPAHQSNMASTPNLSI 355 C.albicans TP PF-033 S. epidermidis MFIFKTTSKSHFHNNVKSLECIKIPINKNR 356 M.luteus E. coli P. aeruginosa C. albicans MRSA S. pneumoniae PF-034 M.luteus EPKKKHFPKMESASSEP 357 PF-035 S. epidermidis SFYESY 358 M. luteusE. coli C. albicans MRSA C. jeikeium C. jejuni PF-036 S. epidermidisILNRLSRIVSNEVTSLIYSLK 359 M. luteus P. mirabilis E. coli C. albicansMRSA S. pneumoniae C. jejuni PF-037 S. epidermidisMTKKRRYDTTEFGLAHSMTAKITLHQA 360 M. luteus LYK P. aeruginosa C. albicansMRSA S. pneumoniae E. faecalis C. jeikeium PF-038 M. luteusMAYKDEGKETKFAVKGYKD 361 PF-039 P. mirabilis MLEEKNKSL 362 C. jeikeiumPF-040 S. epidermidis MIHLTKQNTMEALHFIKQFYDMFFILNF 363 M. luteus NV P.mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E.faecalis C. jeikeium C. jejuni PF-041 MRSA ELLVILPGFI 364 PF-042 S.epidermidis LLLSYFRYTGALLQSLF 365 M. luteus P. mirabilis E. coli P.aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-043M. luteus MIKNETAYQMNELLVIRSAYAK 366 C. jejuni PF-044 S. epidermidisKLKKYIHKPD 367 M. luteus MRSA C. jeikeium PF-045 S. epidermidisLDINDYRSTY 368 E. coli E. faecalis C. jejuni PF-046 E. coliLDFYLTKHLTLML 369 E. faecalis C. jeikeium PF-047 S. mutansNQEPSLQQDKEQKDNKG 370 PF-048 S. epidermidis LYFAFKKYQERVNQAPNIEY 371 M.luteus E. coli MRSA C. jeikeium C. jejuni PF-049 S. epidermidisAYYLKRREEKGK 372 MRSA C. jeikeium C. jejuni PF-050 S. epidermidisSYYLKRREEKGK 373 M. luteus E. coli C. jeikeium PF-051 S. epidermidisRFFNFEIKKSTKVDYVFAHVDLSDV 374 M. luteus P. aeruginosa C. albicans MRSAS. pneumoniae E. faecalis PF-052 S. epidermidis QELINEAVNLLVKSK 375 M.luteus E. coli MRSA E. faecalis C. jeikeium C. jejuni PF-053 S.epidermidis KLFGQWGPELGSIYILPALIGSIILIAIVTL 376 M. luteus ILRAMRK E.coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis PF-054 S.epidermidis VSISRFIGGGHVFNGNNKRNL 377 E. coli PF-055 S. mutansGHVFNGNNKRNL 378 PF-056 S. epidermidis AEQLFGKQKQRGVDLFLNRLTIILSILFF 379M. luteus VLMICISYLGM P. mirabilis E. coli P. aeruginosa C. albicansMRSA S. pneumoniae E. faecalis C. jeikeium PF-057 S. epidermidisTMIVISIPRFEEYMKARHKKWM 380 M. luteus P. mirabilis E. coli P. aeruginosaC. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-058S. epidermidis FADQSQDNA 381 M. luteus E. coli C. albicans MRSA C.jeikeium C. jejuni PF-060 E. coli HSSHL 382 C. albicans C. jeikeiumPF-061 S. epidermidis GYNSYKAVQDVKTHSEEQRVTAKK 383 S. pneumoniae PF-062S. epidermidis MKKKRINNDILGRMIYSSSIDKRNLYNL 384 M. luteus KYYE E. coliP. aeruginosa MRSA S. pneumoniae E. faecalis C. jeikeium PF-063 S.epidermidis IAAIIVLVLFQKGLLQIFNWILIQLQ 385 M. luteus E. coli P.aeruginosa MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-064E. coli DYYGKE 386 PF-065 M. luteus LEKNTRDNYFIHAIDRIYINTSKGLFPES 387 E.coli ELVAWG P. aeruginosa C. albicans MRSA S. pneumoniae C. jeikeium C.jejuni PF-066 M. luteus IKGTVKAVDETTVVITVNGHGTELTFEK 388 E. coliPAIKQVDPS C. jeikeium PF-067 S. epidermidis DLIVKVHICFVVKTASGYCYLNKREAQ389 M. luteus AAI P. mirabilis E. coli P. aeruginosa C. albicans MRSA S.pneumoniae E. faecalis C. jeikeium C. jejuni PF-068 S. epidermidisSHLINNFGLSVINPSTPICLNFSPVFNLLT 390 M. luteus VYGITCN P. mirabilis E.coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C.jeikeium PF-069 E. faecalis FDPVPLKKDKSASKHSHKHNH 391 C. jejuni PF-070S. epidermidis SMVKSEIVDLLNGEDNDD 392 C. jejuni PF-071 S. epidermidisHCVIGNVVDIANLLKRRAVYRDIADVIK 393 E. coli MR P. aeruginosa C. albicansMRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-073 S.epidermidis CPSVTMDACALLQKFDFCNNISHFRHFF 394 M. luteus AIKQPIER P.aeruginosa C. albicans MRSA S. pneumoniae E. faecalis PF-074 S.epidermidis RDIHPIYFMTKD 395 M. luteus MRSA PF-075 M. luteusFVNSLIMKDLSDNDMRFKYEYYNREKDT 396 E. coli P. aeruginosa MRSA C. jeikeiumPF-076 S. epidermidis LYQYELLSKEEYLKCTLIINQRRNEQK 397 M. luteus E. coliP. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C.jejuni PF-097 C. jeikeium QPTQGEQGTRPRRPTPMRGLLI 398 PF-099 S.epidermidis EIIAYLEGRFANA 399 M. luteus E. coli C. jeikeium PF-101 S.mutans DPVPERQEQACACHRTAKPGK 400 PF-104 MRSA ERTAVNDLWI 401 C. jeikeiumPF-123 M. luteus TTRPQVAEDRQLDDALKETFPASDPISP 402 E. coli PF-124 S.epidermidis MADGQIAAIAKLHGVPVATRNIRHFQSF 403 M. luteus GVELINPWSG P.mirabilis E. coli P. aeruginosa C. albicans MRSA E. faecalis C. jejuniPF-125 S. epidermidis YVVGALVILAVAGLIYSMLRKA 404 M. luteus P. mirabilisE. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C.jejuni PF-126 S. epidermidis FSPEAFGIGAAGVLGSFVTGLLIGWVAS 405 M. luteusLLRKAK P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniaeE. faecalis C. jeikeium C. jejuni PF-127 S. epidermidisMLRYLSLFAVGLATGYAWGWIDGLAA 406 M. luteus SLAV E. coli P. aeruginosa C.albicans MRSA S. pneumoniae E. faecalis PF-128 M. luteusGIKVVAARFEEIQFSENFDSIILA 407 P. aeruginosa E. faecalis PF-129 S.epidermidis MKLLARDPWVCAWNDIW 408 MRSA E. faecalis C. jeikeium C. jejuniPF-130 E. faecalis LQRSDEESMPRRHEKYS 409 C. jeikeium C. jejuni PF-131 S.epidermidis RRAAARTKGNRR 410 E. coli MRSA C. jeikeium PF-132 S.epidermidis RPGDGAAEQGRSR 411 C. jeikeium PF-133 S. epidermidisGDPTAGQKPVECP 412 C. jeikeium C. jejuni M. smegmatis PF-134 S.epidermidis GKAMKRQDCSAL 413 C. jeikeium PF-135 S. epidermidisPPARPARIPQTPTLHGASLFRQRS 414 M. luteus E. coli P. aeruginosa MRSA C.jeikeium M. smegmatis PF-136 S. epidermidis LRGRVGRITACGYPP 415 M.luteus P. mirabilis E. coli MRSA E. faecalis C. jeikeium C. jejuni M.smegmatis PF-137 S. epidermidis VLGKGHDLLDVGKTALKSRVFAWLGGS 416 P.mirabilis S. pneumoniae C. jeikeium C. jejuni PF-138 S. epidermidisAVHHSLLFR 417 M. luteus P. mirabilis E. coli C. albicans MRSA C.jeikeium C. jejuni PF-139 S. epidermidis ALSKPAIQARTLCRRQDPP 418 M.luteus P. mirabilis E. coli P. aeruginosa C. albicans S. pneumoniae E.faecalis C. jeikeium C. jejuni PF-140 S. epidermidisFHRRVIRASEWALTTRSFSTPLRSAAR 419 M. luteus P. mirabilis E. coli P.aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C.jejuni M. smegmatis PF-141 S. epidermidis VVRRFQGM 420 M. luteus C.albicans MRSA C. jeikeium PF-142 S. mutans GIDRGCQAAR 421 PF-143 S.epidermidis LSPRPIIVSRRSRADNNNDWSR 422 MRSA C. jeikeium PF-144 S.epidermidis RSGQPVGRPSRRAWLR 423 M. luteus E. coli C. albicans MRSA S.pneumoniae E. faecalis C. jeikeium PF-145 S. epidermidisGIVLTGRAGLVSGACSMALGVGLG 424 M. luteus P. mirabilis E. coli P.aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C.jejuni M. smegmatis PF-146 S. epidermidis GCGKRRIITKSASRDTR 425 M.luteus P. aeruginosa C. albicans MRSA C. jeikeium PF-147 S. epidermidisRRPRRRRSGHGQSASAA 426 M. luteus MRSA PF-148 S. epidermidisRRGCTERLRRMARRNAWDLYAEHFY 427 M. luteus P. mirabilis E. coli P.aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C.jejuni M. smegmatis PF-149 S. epidermidis GKVSVLTRVPRSLGGAPANQ 428 M.luteus E. coli MRSA C. jeikeium PF-150 S. epidermidis EIQAKGTG 429 MRSAPF-151 S. epidermidis EEYPARVPLSGEDVTEARRH 430 MRSA E. faecalis C.jeikeium PF-152 S. epidermidis VGYFIWKDSHSRKG 431 C. albicans MRSA E.faecalis C. jeikeium PF-153 M. luteus GILARADCSQIA 432 P. mirabilis E.coli MRSA PF-154 S. mutans GIKKSKHPSTDDYVVKTTIDSL 433 PF-155 C. jeikeiumGRYGDDSKERQGRAQ 434 PF-156 S. epidermidis LITAEQPATAPIAGK 435 C.jeikeium PF-157 S. epidermidis HTAVVWLAGVSGCVALSHCEPA 436 M. luteus P.mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E.faecalis C. jeikeium C. jejuni PF-158 S. epidermidis VRLESRPADLPE 437PF-159 S. epidermidis TMAFVEKAQLRVPVGDDLPV 438 PF-160 S. epidermidisSFHASLTKNEKPIKSTG 439 PF-161 S. epidermidis RGRALASTATTRPARRRR 440 M.luteus E. coli C. jejuni PF-162 S. epidermidis GIRRLHSVENLNREISHRMAGLR441 MRSA PF-163 S. epidermidis TSWLRAAERQEIGEPTKTFGEKTTSL 442 PF-164 S.epidermidis EEVSRALAGIGLGLGCRIG 443 M. luteus E. coli C. jeikeium PF-165MRSA GPVSVVASLRRGTTVQRHSQNNHNKG 444 C. jejuni KP PF-166 E. coliSKAVSRKRSI 445 C. jeikeium PF-167 S. epidermidis AIEGVIKKGACFKLLRHEMF446 E. coli C. albicans MRSA C. jeikeium C. jejuni PF-168 S. epidermidisVLPFPAIPLSRRRACVAAPRPRSRQRAS 447 M. luteus E. coli C. albicans MRSA C.jeikeium C. jejuni PF-169 S. epidermidis APGSAADSPRSRADD 448 E. coli C.albicans E. faecalis C. jeikeium PF-170 S. epidermidis RLARGRPTNLCGRRG449 M. luteus P. mirabilis E. coli P. aeruginosa C. albicans MRSA S.pneumoniae E. faecalis C. jejuni PF-171 S. epidermidis TQVTLCRTW 450 E.coli P. aeruginosa S. pneumoniae PF-172 S. epidermidisLTGVRRPWRAPWAGTSGWALR 451 M. luteus E. coli P. aeruginosa MRSA E.faecalis C. jejuni PF-173 S. epidermidis AGRTAIVQGGG 452 M. luteus P.mirabilis E. coli P. aeruginosa C. albicans C. jeikeium C. jejuni PF-174S. epidermidis RGGDSPARRRPGLAGPGGPG 453 P. aeruginosa C. jeikeium PF-175S. epidermidis RRRPAGQRPEKASQAMIAA 454 E. faecalis PF-176 S. epidermidisRLTSNQFLTRITPFVFAQH 455 M. luteus P. mirabilis E. coli C. albicans MRSAE. faecalis C. jeikeium PF-177 M. luteus VTSEPGIAHDIRLLPRAAAFR 456 MRSAE. faecalis C. jeikeium PF-178 S. epidermidis EVYSSPTNNVAITVQNN 457 M.luteus B. subtilis P. mirabilis E. coli P. aeruginosa C. albicans MRSAS. pneumoniae E. faecalis C. jeikeium PF-180 S. epidermidisSGLGDLGFSSEAK 458 M. luteus P. aeruginosa C. albicans MRSA E. faecalisC. jejuni M. smegmatis PF-181 S. epidermidis GIAPRRNEWGAVGGR 459 M.luteus E. coli MRSA E. faecalis C. jeikeium PF-182 S. epidermidisLPATRDKTRVPASVAGAP 460 M. luteus E. coli E. faecalis C. jeikeium PF-183S. epidermidis KPGISVENRQ 461 M. luteus E. coli C. albicans MRSA E.faecalis C. jeikeium PF-184 S. epidermidis LIADRHIRA 462 M. luteus E.coli P. aeruginosa C. albicans MRSA C. jeikeium PF-185 E. coliRPAQARQGPGGLIADRHIRA 463 P. aeruginosa PF-186 S. epidermidisDADKNLSLERDRFAWRVAAP 464 M. luteus E. coli P. aeruginosa MRSA C.jeikeium PF-187 S. epidermidis EIQKIAKGVSGQVYGPSRQITISKKR 465 M. luteusE. coli MRSA PF-188 S. epidermidis ARTFAGRLGTRYFGGLMRSTKA 466 M. luteusE. coli C. albicans MRSA E. faecalis PF-189 S. epidermidisGNLTRSREAARATQ 467 M. luteus C. albicans MRSA E. faecalis C. jejuniPF-190 S. epidermidis HFILRKPLLFMIHSLKTGPLDRF 468 M. luteus P. mirabilisE. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C.jeikeium PF-191 E. coli QFCNFAWLFLASNNAQVSALA 469 P. aeruginosa C.jejuni PF-192 S. epidermidis VEEDEAPPPHY 470 M. luteus P. aeruginosa C.albicans E. faecalis C. jeikeium PF-193 S. epidermidis PPHCPPGHAKKGWC471 M. luteus E. coli MRSA E. faecalis C. jejuni PF-194 C. jeikeiumMKGNKLATAHEQPVKNSAPPL 472 PF-195 S. epidermidis EMAEGSADDRLRKTPRDC 473M. luteus E. faecalis C. jeikeium PF-196 S. epidermidisTTARYIRRQCHTSITPLSQG 474 M. luteus P. mirabilis E. coli P. aeruginosa C.albicans MRSA S. pneumoniae E. faecalis C. jejuni PF-197 S. epidermidisCNALLRRGHPPSAL 475 M. luteus C. albicans E. faecalis C. jejuni PF-200 S.epidermidis GIELKSLIMAQIERWRQA 476 M. luteus MRSA E. faecalis C.jeikeium PF-201 S. epidermidis GCRPASLSDADPDGR 477 M. luteus E. coli C.albicans E. faecalis C. jeikeium C. jejuni PF-202 S. epidermidisALNRASLRLALGE 478 M. luteus E. coli MRSA E. faecalis C. jeikeium C.jejuni PF-203 S. epidermidis SWKCHHLAI 479 M. luteus P. mirabilis E.coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jejuniPF-204 S. epidermidis ALQKQDMNLPSVKNQLVFLKSTG 480 P. mirabilis E. coliP. aeruginosa C. albicans C. jejuni PF-205 S. epidermidisAGVLETPRCRGEYGAN 481 M. luteus E. coli P. aeruginosa C. albicans MRSA E.faecalis C. jeikeium C. jejuni PF-206 M. luteus KLRSASKKSLQEKSCGIMPEKPAG482 C. albicans C. jeikeium C. jejuni PF-207 M. luteusAAGCRDLGSLSSLVTNPS 483 C. jeikeium PF-208 S. epidermidisDAYHCHLVRSPDAHDLSMRIGFV 484 C. albicans MRSA S. pneumoniae E. faecalisC. jeikeium C. jejuni PF-209 C. albicans NYAVVSHT 485 C. jeikeium C.jejuni PF-210 S. epidermidis EREDGCDAMPLP 486 P. aeruginosa C. albicansMRSA E. faecalis C. jeikeium C. jejuni PF-211 S. epidermidisDSFDSLSPFRERGGEREDGCDAMPLP 487 M. luteus E. coli P. aeruginosa C.albicans S. pneumoniae E. faecalis C. jeikeium C. jejuni M. smegmatisPF-212 M. luteus NDSKASN 488 P. aeruginosa PF-213 S. epidermidisMTTGVDFIIEKV 489 PF-214 S. mutans GHLRVCWVFSASLLTPFRSATLI 490 S.epidermidis M. luteus E. coli P. aeruginosa A. baumannii PF-215 S.epidermidis ELKITNYNVNTVLYRYYKWGNDLCE 491 M. luteus P. aeruginosa A.baumannii PF-216 S. mutans ESVDKITEALEEDGFPAKVQ 492 E. coli PF-217 S.mutans DWEFTHKTIPQKK 493 PF-218 S. epidermidis SETPEKPVGTFFYSIYYKIIL 494M. luteus P. aeruginosa A. baumannii PF-219 S. epidermidisFLALAVIAGLFKVILIYAAPYLK 495 M. luteus P. aeruginosa A. baumannii PF-221S. epidermidis VFDNIDINF 496 M. luteus P. aeruginosa PF-222 S.epidermidis HIKETR 497 PF-223 S. epidermidis VKFCIECQTKLERKRR 498 M.luteus A. baumannii PF-224 S. epidermidis DYFYITLSQKNTF 499 P.aeruginosa A. baumannii PF-225 S. epidermidis MNCASPEFKKLMELYK 500PF-226 A. baumannii LMFFSENMDKRDTLSGKFRYFAGSKVI 501 KLMNWLSENGK PF-228S. mutans NQLGSQAFAQL 502 PF-229 S. epidermidisDPILIQIGFTRFALRKAEAEKIEIQVEEGV 503 M. luteus PA P. aeruginosa A.baumannii PF-230 S. mutans EDKPTNTIQEIKPVKWQ 504 PF-231 S. mutansAVRDFKKSVREEDEAASLNSPRTIDAQ 505 VKTSESTSVKS PF-232 S. epidermidisFDQLYALEREGKLDELLA 506 M. luteus PF-233 S. epidermidisDANAMARTTIAIVYILALIALTISYSL 507 M. luteus P. aeruginosa A. baumanniiPF-234 S. epidermidis RTPYILRS 508 M. luteus PF-235 S. epidermidisGIPFSKPHKRQVNYMKSDVLAYIEQNK 509 M. luteus MAHTA PF-236 S. mutansKEIRTATVAELNAKRRLTSAEQALAEVS 510 S. epidermidis E. coli C. albicans S.pneumoniae E. faecalis PF-237 S. epidermidis YVKPKVGVHE 511 PF-238 S.mutans RNAVVVTEATFPKYEEEITNYLNRRFGE 512 S. epidermidis DWSLKLEKCSVA E.coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis PF-239 S.mutans PKHNVVTGVSVDLDYKP 513 E. coli PF-240 S. mutans RITEVPPDEHSDR 514E. coli PF-242 S. mutans KLFEDPLIKSKAVENFQTTWHEQCLAK 515 E. coli ELAKNMPF-244 S. epidermidis HMRTISYLLAFAKFSLFIPPKQSLKRL 516 M. luteus P.aeruginosa A. baumannii PF-245 S. epidermidis MNDVKPVVQPKQTLKAFLVQLLSVRA517 M. luteus GVYIKQNNQLPKTKG P. aeruginosa A. baumannii PF-246 S.mutans QPDEKAEFFDPSLDKVYRHPTFYHIPDG 518 IEHM PF-247 S. epidermidisETAASETH 519 PF-248 S. mutans ILSKLWFWMINSLGVVLLVSYWLLAK 520 S.epidermidis WGVA M. luteus E. coli P. aeruginosa A. baumannii PF-249 S.epidermidis INSRYKISF 521 M. luteus PF-252 S. mutansMKKLVAALAVIVILTGCVYDPVNYDKI 522 HDQEFQDHLRQNG PF-253 S. epidermidisVRDDDS 523 M. luteus PF-254 S. epidermidis FIYGVGFVPHFWLWKWLFSPWIAWPL524 M. luteus MLLGYYIWFLT P. aeruginosa A. baumannii PF-255 P.aeruginosa DHKINESQHNPFRSDSNKQNVDFF 525 PF-256 S. epidermidisEYFKQVYVKNEKIYSFWICKDLSPKEA 526 AKRAEDILVKLK PF-257 S. epidermidisVWENRKKYLENEIERHNVFLKLGQEVI 527 KGLNALASRGR PF-259 S. epidermidisLPFSKIGRRVSYKKKDVLKYEQSKTVL 528 P. aeruginosa NTAQLATV A. baumanniiPF-262 S. mutans DPHSEIDVTRYCQLHHFTCQTMQISERE 529 S. epidermidisFHYLIETQ M. luteus E. coli P. aeruginosa A. baumannii PF-263 S.epidermidis NLKKCPC 530 M. luteus A. baumannii PF-265 S. epidermidisMKTLFFPLFLIIFVLIIQALDQSYQKKIGI 531 M. luteus SKPQKHPEFMQ A. baumanniiPF-266 S. mutans DQEKKNKTEESTEQ 532 PF-267 M. luteus SDDKRTD 533 PF-268S. mutans EVLLSDLRPDIFSET 534 PF-270 S. epidermidisMYLTPYAWIAVGSIFAFSVTTIKIGDQN 535 M. luteus DEKQKSHKNDVHKR P. aeruginosaPF-271 S. epidermidis AAQPQTTSP 536 M. luteus P. aeruginosa A. baumanniiPF-273 S. epidermidis LVGALLIFVALIYMVLKGNADKN 537 M. luteus P.aeruginosa A. baumannii PF-275 S. mutans LVSGVANTVKNTAHTVGNTAKHAGHV 538AADTTVKATKKQQVK PF-276 S. epidermidis LDLALSTNSLNLEGFSF 539 PF-278 M.luteus LSLATFAKIFMTRSNWSLKRFNRL 540 A. baumannii PF-279 S. mutansSHIGFISISACLAVLLGIARLFVWTWVKF 541 S. epidermidis FA M. luteus E. coli P.aeruginosa A. baumannii PF-281 S. mutans SYNTYYNKLIHGQRTPDGM 542 E. coliPF-282 S. mutans QNNDTSAWCGSAHKNGNS 543 PF-283 B. subtilisMIRIRSPTKKKLNRNSISDWKSNTSGRF 544 B. fragilis FY C. difficile PF-284 C.difficile MRYITYSLIPRLLSKKVIHQQ 545 PF-285 S. mutans VPAKLLRVIDEIPE 546PF-288 S. mutans IYQLLNIEYSEDD 547 E. coli PF-289 C. difficileMGRHLWNPSYFVATVSENTEEQIRKYR 548 KNK PF-291 S. mutans DVDGAIESEL 549 E.coli PF-292 S. epidermidis SFVSTTVRLIFEESKRYKF 550 B. subtilis B.fragilis PF-294 S. epidermidis DFLVNFLWFKGELNWGKKRYK 551 C. difficilePF-295 C. difficile NIQVYESECGNYIFKKSDESFLIDIFDKN 552 GTH PF-297 S.epidermidis ISKGIDDIVYVINKILSIGNIFKIIKRK 553 B. subtilis B. fragilisPF-299 B. subtilis LATKLKYEKEHKKM 554 PF-300 B. subtilis VKDVLLELFNKIIGA555 C. difficile PF-301 C. difficile GIVLIGLKLIPLLANVLN 556 PF-304 S.mutans LVKDTSDIKNDLNNIEIVTSKNSNDIAKL 557 KSVK PF-305 C. difficileMREWICPSCNETHDRDINASINILKEGL 558 RLITIQNK PF-306 C. difficileGCILPHKKDNYNYIMSKFQDLVKITSKK 559 PF-307 S. epidermidisMKRRRCNWCGKLFYLEEKSKEAYCCK 560 B. subtilis ECRKKAKKVKK B. fragilis C.difficile PF-308 C. difficile QQYLILDRM 561 PF-309 S. mutansGIPGMTAAPAEENEQEENADEE 562 E. coli PF-311 C. difficileIDAVTKKKTTCMIRAPTKIPIAHTDN 563 PF-313 S. epidermidisYITSHKNARAIIKKFERDEILEEVITHYL 564 C. difficile NRK PF-314 S. mutansECLKKAIKSKALNKAFKIDVPDEVYDN 565 LLMELEEYEK PF-317 S. mutans LILVSDI 566PF-319 S. epidermidis SIGSMIGMYSFRHKTKHIKFTFGIPFILFL 567 B. subtilisQFLLVYFYILK C. difficile PF-320 S. mutans DSGYYALLENKEERVVWDGEVVANNI 568E. coli FNNLWIVVNKVKTG PF-323 S. mutans ARESIEKSHVPVDATIVGVVDSFEVFDE 569PF-324 C. difficile HFSLL 570 PF-325 S. mutans LTIDEKLRNHR 571 E. coliPF-326 S. mutans VIVGNLGAQKEKRNDTPISAKKDIMGD 572 E. coli KTVRVRADLHHPF-328 S. mutans NGNEKAFSEVENLVK 573 PF-329 S. epidermidis IGILFDKSVRKY574 PF-333 S. mutans YMTKKLVEMAEQQMAGKSNR 575 PF-334 S. epidermidisQQYLILDRM 576 C. difficile PF-336 S. mutans MLTSRKKRLKKIVEEQNKKDESI 577E. coli PF-337 S. epidermidis YMTKKLVEMAERQMAGK 578 PF-338 S. mutansKGTSCPDQLSKAIRQSI 579 PF-340 S. mutans VKDVLLELFNKIIGA 580 E. coliPF-344 B. subtilis DERLPEAKAIRNFNGSVMVLGR 581 C. jejuni PF-347 S.epidermidis GIFTGVTVVVSLKHC 582 B. subtilis B. fragilis E. coli P.aeruginosa C. albicans MRSA S. pneumoniae E. faecalis PF-348 B. subtilisESASAAEWYNPNMNVKKAICMG 583 E. coli P. aeruginosa C. albicans E. faecalisC. jejuni PF-349 S. epidermidis MPKSCHVPVLCDFFFLVIIKFLALFKTIQS 584 B.subtilis B. fragilis E. coli P. aeruginosa C. albicans MRSA S.pneumoniae E. faecalis C. jeikeium PF-350 S. epidermidis LAVILRAIVY 585E. coli E. faecalis C. jeikeium C. jejuni PF-351 S. mutansYLFFKGKKVAEEEATKDEVKR 586 PF-352 C. jeikeium RVKKIG 587 PF-353 S.epidermidis EKTNFKGVKRNFYKKASFFV 588 M. luteus B. subtilis E. coli C.albicans S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-354 S.epidermidis FTFSKCRASNGRGFGTLWL 589 B. subtilis E. coli P. aeruginosa C.albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-355 S.epidermidis WIAIGLLLYFSLKNQ 590 B. subtilis B. fragilis E. coli P.aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-356S. epidermidis VSIKIGAIVIGMIGLMELLTE 591 B. subtilis B. fragilis E. coliP. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeiumPF-357 S. epidermidis MLTIIIGFIFWTMTLMLGYLIGEREGRK 592 M. luteus HE P.mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E.faecalis C. jeikeium PF-358 S. epidermidis RNTAHNIKWRSKN 593 B. subtilisE. coli C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuniPF-359 S. epidermidis MTVMEDPGSEQRNKIQSPMKGEDFSAL 594 B. fragilis FGR P.aeruginosa C. albicans MRSA E. faecalis C. jeikeium PF-360 S.epidermidis MEQKVKVIFVPRSKPDNQLKTFVSAVL 595 B. subtilis FKA E. coli P.aeruginosa C. albicans E. faecalis C. jeikeium C. jejuni PF-361 S.epidermidis NQVTEGIRLLVE 596 E. coli E. faecalis C. jejuni PF-362 S.epidermidis NIERILKEKVWMIRCVE 597 E. coli P. aeruginosa C. albicans E.faecalis C. jejuni PF-363 B. subtilis SMLSVTVMCLMHASVAANQAMEKKV 598 E.coli P. aeruginosa C. albicans S. pneumoniae E. faecalis PF-364 S.epidermidis LVNGIKI 599 B. fragilis P. aeruginosa C. jeikeium C. jejuniPF-365 S. epidermidis LYKQKIQLEEELEKLKDDRQ 600 B. subtilis B. fragilisP. aeruginosa C. albicans PF-366 S. epidermidis ALCSVIKAIELGIINVHLQ 601M. luteus B. fragilis P. mirabilis E. coli P. aeruginosa C. albicansMRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-367 B. subtilisTKTPGTFTPGTGIQKTAVPL 602 PF-368 C. jeikeium MLKQTA 603 C. jejuni PF-369B. subtilis MSEAVNLLRGARYSQRYAKNQVPYEVI 604 B. fragilis IEK E. coli P.aeruginosa C. albicans S. pneumoniae C. jeikeium C. jejuni PF-370 S.epidermidis VIFLHKESGNLKEIFY 605 E. coli P. aeruginosa E. faecalis C.jejuni PF-371 S. epidermidis TFIYNEF 606 B. fragilis C. jejuni PF-372 C.jeikeium KKQDKRIEDKYKRMKKGD 607 C. jejuni PF-373 S. epidermidis HFYLLFER608 E. coli P. aeruginosa C. albicans MRSA E. faecalis C. jejuni PF-374S. epidermidis HLFFVKGMFILCQKNQINDE 609 B. subtilis B. fragilis E. coliP. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C.jejuni PF-375 S. epidermidis MDSAKAQTMRTDWLAVSCLVASAYLR 610 B. subtilisSMLA B. fragilis E. coli P. aeruginosa C. albicans S. pneumoniae E.faecalis C. jeikeium C. jejuni PF-376 S. epidermidisMTVFEALMLAIAFATLIVKISNKNDKK 611 B. subtilis B. fragilis E. coli P.aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C.jejuni PF-378 B. subtilis ESAKSNLNFLMQEEWALFLLL 612 B. fragilis E. coliP. aeruginosa C. jeikeium PF-379 S. epidermidis VFVVLFIIYLASKLLTKLFPIKK613 B. subtilis B. fragilis E. coli P. aeruginosa C. albicans MRSA S.pneumoniae E. faecalis C. jeikeium C. jejuni PF-380 S. epidermidisKKIIPLITLFVVTLVG 614 B. subtilis B. fragilis E. coli P. aeruginosa C.albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-381 E.coli QGANPCQQVGFTVNDPDCRLAKTV 615 P. aeruginosa C. jejuni PF-382 S.epidermidis KYKCSWCKRVYTLRKDHKTAR 616 B. subtilis B. fragilis E. coli P.aeruginosa E. faecalis C. jeikeium C. jejuni PF-383 S. epidermidisWSEIEINTKQSN 617 B. subtilis B. fragilis E. coli C. jejuni PF-384 E.faecalis HISKERFEAY 618 C. jeikeium C. jejuni PF-385 S. epidermidisMIKKSILKIKYYVPVLISLTLILSA 619 E. coli P. aeruginosa C. albicans E.faecalis PF-386 S. epidermidis FTLTLITTIVAILNYKDKKK 620 B. subtilis B.fragilis E. coli P. aeruginosa C. albicans S. pneumoniae E. faecalis C.jeikeium C. jejuni PF-387 B. subtilis GAVGIAFFAGNMKQDKRIADRQNKKSE 621 E.coli KK P. aeruginosa E. faecalis C. jeikeium C. jejuni PF-388 E.faecalis ITPLLDEIGKVCIDKISK 622 C. jeikeium C. jejuni PF-389 S.epidermidis GLQFKEIAEEFHITTTALQQWHKDNGY 623 C. albicans PIYNKNNRK MRSAS. pneumoniae E. faecalis C. jeikeium PF-390 S. epidermidisVVAYVITQVGAIRF 624 P. aeruginosa C. albicans MRSA PF-392 S. epidermidisDPAGCNDIVRKYCK 625 B. subtilis S. pneumoniae C. jeikeium C. jejuniPF-393 S. epidermidis DLVQSILSEFKKSG 626 E. coli C. albicans MRSA S.pneumoniae C. jejuni PF-394 S. epidermidis VLKEECYQKN 627 MRSA C. jejuniPF-395 S. epidermidis YCVPLGNMGNMNNKIW 628 E. coli P. aeruginosa S.pneumoniae E. faecalis C. jeikeium C. jejuni PF-396 S. epidermidisLIYTILASLGVLTVLQAILGREPKAVKA 629 E. coli P. aeruginosa C. albicans E.faecalis C. jeikeium PF-397 S. epidermidis VEDLMEDLNA 630 MRSA S.pneumoniae E. faecalis C. jejuni PF-398 S. epidermidisILVVLAGILLVVLSYVGISKFKMNC 631 B. subtilis B. fragilis E. coli P.aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C.jejuni PF-399 S. epidermidis FPIISALLGAIICIAIYSFIVNRKA 632 M. luteus P.mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E.faecalis C. jejuni PF-400 S. epidermidis VIAWKFRNKFENSGV 633 E. coli S.pneumoniae E. faecalis C. jeikeium PF-401 S. epidermidisYWLSRVTTGHSFAFEKPVPLSLTIK 634 E. coli P. aeruginosa MRSA E. faecalis C.jejuni PF-402 S. epidermidis FIDVLKSKINEFLN 635 P. aeruginosa E.faecalis C. jejuni PF-403 E. coli LLSTEQLLKYYDGETFDGFQLPSNE 636 P.aeruginosa S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-404 S.epidermidis VLYFQATVV 637 E. coli P. aeruginosa E. faecalis C. jeikeiumC. jejuni PF-405 S. epidermidis LVRIEVDDLEEWYERNFI 638 E. coli E.faecalis PF-406 E. coli YLEMNADYLSNMDIFDELWEKYLENNK 639 C. jejuni PF-407S. epidermidis KPKNKKEKTVISYEKLLSMY 640 B. subtilis E. coli P.aeruginosa MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-408S. epidermidis YCVPLGNMGNMNNKIW 641 E. coli P. aeruginosa MRSA E.faecalis C. jeikeium C. jejuni PF-409 S. epidermidis DLVQSILSEFKKSG 642MRSA C. jeikeium C. jejuni PF-410 S. epidermidis FALELIALCRNLFIVYFP 643M. luteus B. fragilis P. mirabilis E. coli P. aeruginosa C. albicansMRSA S. pneumoniae E. faecalis PF-411 M. luteus WVAVAILLNIALQTQLT 644 B.subtilis B. fragilis P. mirabilis P. aeruginosa C. albicans MRSA S.pneumoniae E. faecalis C. jeikeium C. jejuni PF-412 M. luteus TSGWLGQLEQ645 E. coli C. albicans C. jeikeium C. jejuni PF-413 P. aeruginosaTFAGSIKIGVPDLVHVTFNCKR 646 C. albicans C. jejuni PF-414 E. coli LLNKKLE647 C. albicans C. jeikeium PF-416 S. pneumoniae SKAGLYGKIERSDKRE 648 C.jeikeium PF-417 S. epidermidis DSYFRS 649 C. jeikeium C. jejuni PF-418S. epidermidis FFLVHFYIRKRKGKVSIFLNYF 650 M. luteus P. mirabilis E. coliP. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C.jejuni PF-421 C. jeikeium KHCFEITDKTDVV 651 PF-422 C. albicansMSRKKYENDEKSQKKLKIGRKSDVFYG 652 MRSA IID C. jeikeium PF-423 S.epidermidis AGKKERLLSFREQFLNKNKKK 653 M. luteus E. coli S. pneumoniae E.faecalis C. jeikeium PF-424 S. epidermidis IAAFVTSRAFSDTVSPI 654 C.albicans MRSA PF-425 S. epidermidis MMELVLKTIIGPIVVGVVLRIVDKWLN 655 M.luteus KDK E. coli P. aeruginosa C. albicans MRSA S. pneumoniae C.jeikeium PF-426 S. epidermidis MLQKYTQMISVTKCIITKNKKTQENVD 656 E. coliAYN P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeiumPF-427 M. luteus YVLEYHGLRATQDVDAFMAL 657 P. aeruginosa C. albicans C.jejuni PF-428 S. epidermidis ENEESIF 658 C. albicans E. faecalis C.jeikeium PF-429 S. epidermidis AATLICVGSGIMSSL 659 S. pneumoniae C.jeikeium PF-430 S. epidermidis AVVCGYLAYTATS 660 M. luteus E. coli S.pneumoniae E. faecalis C. jeikeium C. jejuni PF-431 S. epidermidisVAYAAICWW 661 M. luteus E. coli P. aeruginosa MRSA S. pneumoniae E.faecalis C. jeikeium C. jejuni PF-432 S. epidermidis FNGDSEFFLCIAF 662M. luteus E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E.faecalis C. jeikeium C. jejuni PF-433 S. epidermidisMRKEFHNVLSSGQLLADKRPARDYNRK 663 E. coli S. pneumoniae C. jeikeium PF-434S. epidermidis GQLLADKRPARDYNRK 664 M. luteus S. pneumoniae C. jeikeiumPF-435 C. jeikeium MSRWDGHSDKGEAPAGKPPMHGFGLN 665 GENK PF-436 C.jeikeium KKHVLVGKQEKNG 666 PF-438 S. epidermidisQPYFQNQFKKITGYTPLQYRKEKR 667 E. coli S. pneumoniae C. jeikeium C. jejuniPF-439 S. epidermidis RVLVLKKFHGIMDGNRNVAVFFVGQ 668 M. luteus B.fragilis P. mirabilis E. coli P. aeruginosa C. albicans MRSA S.pneumoniae E. faecalis C. jeikeium C. jejuni PF-440 S. epidermidisMFIISPDLFNIAVILYILFFIHDILLLILS 669 M. luteus P. mirabilis E. coli P.aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C.jejuni PF-441 C. jeikeium TQVHKMARGIDPGPANGIYR 670 PF-442 S. epidermidisMQIFYIKTKIFLSFFLFLLIFSQCFYKIEE 671 E. coli C. albicans S. pneumoniae E.faecalis PF-443 S. epidermidis KLLYFFNYFENLQQVHLLVQL 672 M. luteus P.mirabilis E. coli P. aeruginosa C. albicans S. pneumoniae E. faecalis C.jeikeium C. jejuni PF-444 M. luteus MAAKLWEEGKMVYASSASMTKRLKL 673 C.albicans AMSKV S. pneumoniae C. jeikeium PF-445 M. luteus ASMTKRLKLAMSKV674 S. pneumoniae C. jeikeium PF-446 M. luteus SGNEKV 675 C. jeikeiumPF-447 S. epidermidis IDKSRNKDQFSHIFGLYNICSG 676 M. luteus E. coli S.pneumoniae PF-448 S. epidermidis SLQSQLGPCLHDQRH 677 M. luteus P.mirabilis E. coli S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-450S. epidermidis HRNLIILQRTIFI 678 M. luteus E. coli P. aeruginosa C.albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-451 S.epidermidis MVNYIIGSYMLYREQNNNEALRKFDIT 679 M. luteus LAM E. coli P.aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C.jejuni M. smegmatis PF-452 M. luteus MNNWIKVAQISVTVINEVIDIMKEKQN 680 P.aeruginosa GGK C. albicans S. pneumoniae E. faecalis C. jeikeium M.smegmatis PF-453 M. luteus IIQDIAHAFGY 681 E. coli P. aeruginosa S.pneumoniae E. faecalis C. jeikeium C. jejuni PF-454 S. epidermidisMSVFVPVTNIFMFIMSPIFNVNLLHFKV 682 M. luteus YI E. coli P. aeruginosa C.albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni M.smegmatis PF-456 C. albicans TCVKPRTIN 683 MRSA E. faecalis C. jeikeiumC. jejuni PF-457 C. albicans INKYHHIA 684 S. pneumoniae E. faecalis C.jeikeium PF-458 S. epidermidis ISLIIFIMLFVVALFKCITNYKHQS 685 M. luteusE. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C.jeikeium C. jejuni PF-459 P. aeruginosa EKRMSFNENQSHRPLL 686 PF-460 S.epidermidis MEHVLPFQNTPPNIVIIYKDFTHLKSITFS 687 M. luteus P. mirabilis E.coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C.jeikeium C. jejuni M. smegmatis PF-461 E. coliMTLAIKNCSVTKCLGFGDFVNDDSDSY 688 S. pneumoniae FDA PF-462 E. faecalisKNKTDTL 689 C. jeikeium PF-463 S. epidermidisMVILVFSLIFIFTDNYLVYQSKSIKEDVMI 690 E. coli P. aeruginosa C. albicans S.pneumoniae E. faecalis M. smegmatis PF-464 S. epidermidis VDMVNRFLGN 691C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-465S. epidermidis KPVGKALEEIADGKIEPVVPKEYLG 692 M. luteus E. coli P.aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C.jejuni PF-466 MRSA VRKSDQ 693 C. jeikeium C. jejuni PF-467 MRSAYYKDYFKEI 694 E. faecalis C. jeikeium C. jejuni PF-469 S. epidermidisYKVNYNNIDNHFNTLRH 695 M. luteus P. mirabilis E. coli C. albicans MRSA S.pneumoniae E. faecalis C. jeikeium C. jejuni PF-470 M. luteusPYSDSYATRPHWEQHRAR 696 E. coli MRSA E. faecalis C. jeikeium C. jejuniPF-471 S. epidermidis MVGKIRGVTPRNDLLNANITGQLNLNY 697 M. luteus RLI E.coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C.jeikeium C. jejuni PF-472 S. epidermidis MHISHLLDEVEQTEREKAVNVLENMNG 698E. coli NVI P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C.jeikeium PF-473 S. epidermidis MAADIISTIGDLVKWIIDTVNKFKK 699 E. coli P.aeruginosa C. albicans MRSA S. pneumoniae E. faecalis PF-474 S.epidermidis MHRNLVLVKMEPIPHIMIIANQIGIIIEKA 700 M. luteus P. mirabilis E.coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C.jeikeium C. jejuni M. smegmatis PF-475 S. epidermidisMREKVRFTQAFKLFWTNYFNFKGRSRR 701 M. luteus SEY P. mirabilis E. coli P.aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C.jejuni PF-476 M. luteus WADAQYKLCENCSE 702 P. mirabilis C. albicans S.pneumoniae E. faecalis C. jeikeium C. jejuni PF-477 S. epidermidisHKNKLNIPHIKS 703 M. luteus C. albicans S. pneumoniae C. jeikeium C.jejuni PF-478 S. epidermidis HLFILKSHLKPFPPFRYTYD 704 M. luteus P.mirabilis E. coli C. albicans S. pneumoniae E. faecalis C. jeikeium C.jejuni PF-479 S. epidermidis AYILKRREEKNK 705 M. luteus P. mirabilis E.coli C. albicans S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-480S. epidermidis MVEILVNTAISVYIVALYTQWLSTRDNL 706 M. luteus KA P.mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E.faecalis C. jeikeium C. jejuni M. smegmatis PF-481 C. jeikeiumDELYEIMDKVIEEFNKDIEQNNNNGNN 707 EDLTENKIN PF-482 S. epidermidisLVGYVRTSGTVRSYKIN 708 M. luteus P. mirabilis E. coli P. aeruginosa C.albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-483 P.mirabilis EDNKDKKDKKDK 709 C. jeikeium C. jejuni PF-484 S. epidermidisHKKDIRKQVFKN 710 M. luteus P. mirabilis E. coli E. faecalis C. jeikeiumC. jejuni PF-486 S. mutans MQKEGEEDY 711 PF-487 S. mutansMYKAIAVLAMTIMAFFIFVYPFFIVGLILG 712 E. coli PF-488 S. mutansYPNEQGHHKNNLKNIIIE 713 E. coli PF-489 S. mutans KVDRVSTTITEKIK 714PF-490 S. mutans RLILVSGNATVQK 715 E. coli PF-491 S. mutansIHQYSSKPDIVGQEAKTVQQINS 716 E. coli PF-492 S. mutans IQIDAASFYSISKSTIK717 B. subtilis E. coli PF-493 S. mutans PGAFFFCRGRGCWCGIGW 718 B.subtilis E. coli PF-494 S. mutans FTEPLRPLQAKGQIISIKPSTSSS 719 PF-495 S.mutans KGIYKKRTY 720 E. coli PF-496 S. mutans EVTKRLVALAQQQLRG 721 E.coli PF-497 S. mutans LVLRICTDLFTFIKWTIKQRKS 722 B. subtilis E. coliPF-498 S. mutans MSEEEEVSEKVYNYLRRNEFFEVRKEE 723 E. coli FSA PF-499 S.mutans VYSFLYVLVIVRKLLSMKKRIERL 724 E. coli PF-500 S. mutansMGIFKEEKIKFIDCKGEEVILKIKIKDIKK 725 E. coli PF-501 S. mutansGSTAHKSPIGSTNNQWGMKKTPTD 726 PF-502 S. mutans NKGKQMQDQTGKQPIVDNG 727PF-503 S. mutans VVTLKDIVAVIEDQGYDVQ 728 PF-504 S. mutansILSVELSTKTSASGS 729 E. coli PF-505 S. mutans GYTKDPGTGI 730 PF-506 S.mutans SGRGFALIVVLFILLIIVGAACIR 731 E. coli PF-507 S. mutansLALSIANLFKKKA 732 E. coli PF-508 S. mutans VSTFGKVVKVVDEK 733 PF-509 S.mutans EAKVQAKGEQIACNNY 734 B. subtilis E. coli PF-510 S. mutansWYLYKKQSNQNDRGIPK 735 E. coli PF-511 E. coli VMQSLYVKPPLILVTKLAQQN 736P. aeruginosa S. pneumoniae C. jeikeium PF-512 S. pneumoniaeSFMPEIQKNTIPTQMK 737 C. jeikeium PF-513 C. albicans SNGVGLGVGIGSGIRF-NH2738 PF-514 S. epidermidis QRFYKLFYHIDLTNEQALKLFQVK 739 E. coli P.aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-515S. epidermidis DKSTQDKDIKQAKLLAQELGL-NH2 740 C. albicans S. pneumoniaeC. jeikeium PF-517 C. jejuni VKPTMTASLISTVC 741 PF-518 S. epidermidisSFYSKYSRYIDNLAGAIFLFF 742 E. coli P. aeruginosa C. albicans MRSA S.pneumoniae E. faecalis PF-519 M. luteus YLVYSGVLATAAAF-NH2 743 E.faecalis C. jeikeium PF-520 S. epidermidis LGLTAGVAYAAQPTNQPTNQPTNQPTN744 M. luteus QPTNQPTNQPRW-NH2 E. coli C. albicans MRSA S. pneumoniae E.faecalis C. jeikeium C. jejuni PF-521 S. epidermidis CGKLLEQKNFFLKTR 745E. coli P. aeruginosa S. pneumoniae E. faecalis PF-522 S. epidermidisFELVDWLETNLGKILKSKSA-NH2 746 E. coli P. aeruginosa S. pneumoniae E.faecalis PF-523 S. epidermidis ASKQASKQASKQASKQASKQASRSLKN 747 M. luteusHLL C. albicans S. pneumoniae C. jeikeium C. jejuni PF-524 S.epidermidis PDAPRTCYHKPILAALSRIVVTDR 748 E. coli P. aeruginosa C.albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-526 S.epidermidis VLLLFIFQPFQKQLL-NH2 749 E. coli P. aeruginosa C. albicansMRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-527 S.epidermidis GSVIKKRRKRMAKKKHRKLLKKTRIQR 750 M. luteus RRAGK P. mirabilisE. coli P. aeruginosa MRSA S. pneumoniae E. faecalis C. jeikeium C.jejuni PF-528 S. epidermidis LVDVVVLIRRHLPKSCS-NH2 751 P. aeruginosa C.albicans MRSA S. pneumoniae E. faecalis PF-529 S. epidermidisLSEMERRRLRKRA-NH2 752 E. coli C. albicans MRSA S. pneumoniae E. faecalisC. jeikeium PF-537 S. epidermidis LANDYYKKTKKSW 753 M. luteus P.mirabilis E. coli C. albicans MRSA S. pneumoniae E. faecalis C. jeikeiumPF-539 S. epidermidis SIILTKKKRRKIPLSIDSQIYKYTFKQ 754 M. luteus B.subtilis P. mirabilis E. coli P. aeruginosa C. albicans MRSA S.pneumoniae E. faecalis C. jeikeium PF-540 C. albicansKSILILIKVIFIGQTTIIL 755 PF-542 C. jeikeium KKDNPSLNDQDKNAVLNLLALAK 756PF-543 S. epidermidis NILFGIIGFVVAMTAAVIVTAISIAK 757 M. luteus B.subtilis P. mirabilis E. coli P. aeruginosa C. albicans MRSA S.pneumoniae E. faecalis C. jeikeium PF-544 S. epidermidisFGEKQMRSWWKVHWFHP 758 M. luteus P. mirabilis P. aeruginosa MRSA S.pneumoniae E. faecalis C. jeikeium C. jejuni PF-545 S. epidermidisRESKLIAMADMIRRRI-NH2 759 E. coli P. aeruginosa S. pneumoniae E. faecalisC. jeikeium PF-546 S. epidermidis PIIAPTIKTQIQ 760 E. coli C. albicansS. pneumoniae E. faecalis C. jeikeium PF-547 S. epidermidisWSRVPGHSDTGWKVWHRW-NH2 761 E. coli P. aeruginosa C. albicans MRSA S.pneumoniae E. faecalis PF-548 M. luteus ARPIADLIHFNSTTVTASGDVYYGPG 762P. mirabilis E. coli P. aeruginosa C. albicans S. pneumoniae E. faecalisC. jeikeium C. jejuni PF-549 E. coli TGIGPIARPIEHGLDS 763 C. albicans S.pneumoniae C. jeikeium PF-550 S. pneumoniae STENGWQEFESYADVGVDPRRYVPL764 PF-551 S. pneumoniae QVKEKRREIELQFRDAEKKLEASVQAE 765 PF-552 S.pneumoniae ELDKADAALGPAKNLAPLDVINRS 766 PF-553 S. epidermidisLTIVGNALQQKNQKLLLNQKKITSLG 767 E. coli P. aeruginosa C. albicans MRSA S.pneumoniae C. jeikeium PF-554 S. pneumoniae AKNFLTRTAEEIGEQAVREGNINGP768 PF-555 MRSA EAYMRFLDREMEGLTAAYNVKLFTEAIS 769 S. pneumoniae C.jeikeium PF-556 S. epidermidis SLQIRMNTLTAAKASIEAA 770 M. luteus B.fragilis P. mirabilis E. coli P. aeruginosa C. albicans MRSA S.pneumoniae E. faecalis PF-557 S. pneumoniae AANKAREQAAAEAKRKAEEQAR 771PF-558 S. epidermidis ADAPPPLIVRYS 772 E. coli C. albicans C. jeikeiumC. jejuni PF-559 S. epidermidis SRPGKPGGVSIDVSRDRQDILSNYP 773 M. luteusC. albicans C. jeikeium C. jejuni PF-560 S. epidermidisFGNPFRGFTLAMEADFKKRK 774 M. luteus E. coli S. pneumoniae C. jeikeium C.jejuni PF-562 S. epidermidis TPEQWLERSTVVVTGLLNRK 775 M. luteus P.mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E.faecalis C. jeikeium C. jejuni PF-563 S. epidermidisRPELDNELDVVQNSASLDKLQASYN 776 M. luteus C. jeikeium PF-564 S.epidermidis TIILNDQINSLQERLNKLNAETDRR 777 C. albicans S. pneumoniae C.jeikeium PF-566 P. mirabilis EAQQVTQQLGADFNAITTPTATKV 778 S. pneumoniaePF-567 S. epidermidis QQRVKAVDASLSQVSTQVSGAVASA 779 P. aeruginosa C.albicans MRSA S. pneumoniae C. jeikeium PF-568 S. epidermidisTQAVQVKTAQAQQQ 780 PF-569 M. luteus KSKISEYTEKEFLEFVEDIYTNNK 781 P.mirabilis S. pneumoniae E. faecalis C. jeikeium PF-570 S. pneumoniaeKKFPTEESHIQAVLEFKKLTEHPSG 782 C. jeikeium PF-572 S. epidermidisWRASKGLPGFKAG 783 M. luteus E. coli S. pneumoniae C. jeikeium PF-573 S.epidermidis EKKLIVKLIDSIGKSHEEIVGAG 784 S. pneumoniae PF-575 M. luteusLNFRAENKILEKIHISLIDTVEGSA 785 E. coli C. albicans MRSA S. pneumoniae E.faecalis C. jeikeium PF-576 M. luteus AYSGELPEPLVRKMSKEQVRSVMGK 786 P.mirabilis E. coli P. aeruginosa C. albicans S. pneumoniae PF-577 S.epidermidis PFETRESFRVPVIGILGGWDYFMHP 787 M. luteus P. mirabilis E. coliP. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis PF-578 S.epidermidis QKANLRIGFTYTSDSNVCNLTFALLGSK 788 M. luteus P. mirabilis P.aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-579S. epidermidis MILVCAAVIWGRVLFILKFPIYFSIRLAFL 789 M. luteus P. mirabilisE. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C.jeikeium C. jejuni PF-580 S. epidermidis EILNNNQVIKELTMKYKTQFESNLGGW 790M. luteus TARARR E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E.faecalis C. jeikeium PF-581 S. epidermidis WTARARR 791 M. luteus E. coliP. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeiumPF-583 S. epidermidis KFQGEFTNIGQSYIVSASHMSTSLNTGK 792 M. luteus E. coliP. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeiumPF-584 S. epidermidis SYIKNLSNQKFLIAF 793 M. luteus P. mirabilis C.albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-585 S.epidermidis DYNHLLNVVQDWVNTN 794 E. coli C. albicans MRSA S. pneumoniaeC. jeikeium PF-586 S. epidermidis FFNQANYFFKEF 795 M. luteus E. coli P.aeruginosa MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-587S. epidermidis ASGKYQSYLLNVYVDSKKDRLDIFDKL 796 M. luteus KAKAKFVL E.coli MRSA S. pneumoniae E. faecalis C. jeikeium PF-588 S. epidermidisESVEAIKAKAIK 797 E. coli C. albicans E. faecalis C. jeikeium C. jejuniPF-589 S. epidermidis APLRIDEIRNSNVIDEVLDCAPKKQEHFF 798 C. albicansVVPKIIE MRSA S. pneumoniae PF-590 S. epidermidis YYQAKLFPLL 799 M.luteus E. coli E. faecalis C. jeikeium PF-592 S. epidermidisIMKNYKYFKLFIVKYALF 800 M. luteus P. mirabilis E. coli P. aeruginosa C.albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-593 C.jeikeium MEISTLKKEKLHVKDELSQYLANYKK 801 PF-594 C. jeikeium IVSAIV 802PF-595 S. epidermidis LQNKIYELLYIKERSKLCS 803 M. luteus P. mirabilis E.coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C.jeikeium C. jejuni PF-596 S. epidermidis SKMWDKILTILILILELIRELIKL 804 M.luteus P. mirabilis E. coli P. aeruginosa MRSA E. faecalis C. jeikeiumC. jejuni PF-597 P. mirabilis DEIKVSDEEIEKFIKENNL 805 PF-598 S.epidermidis MKFMLEVRNKAISAYKEITRTQI 806 M. luteus P. mirabilis P.aeruginosa C. albicans MRSA S. pneumoniae C. jeikeium PF-599 S.epidermidis LFEIFKPKH 807 P. mirabilis E. coli C. albicans MRSA S.pneumoniae C. jeikeium PF-600 S. epidermidisTKKIELKRFVDAFVKKSYENYILERELK 808 M. luteus KLIKAINEELPTK B. subtilis P.mirabilis E. coli P. aeruginosa MRSA S. pneumoniae E. faecalis C.jeikeium PF-601 C. jeikeium YRVTVKALE 809 PF-602 P. mirabilisLEKEKKEYIEKLFKTK 810 C. jeikeium PF-603 S. epidermidisIDKLKKMNLQKLSYEVRISQDGKSIYAR 811 M. luteus IK B. subtilis E. coli P.aeruginosa MRSA S. pneumoniae E. faecalis C. jeikeium PF-604 S.epidermidis LMEQVEV 812 C. albicans C. jeikeium PF-605 S. epidermidisHYRWNTQWWKY 813 M. luteus P. mirabilis E. coli P. aeruginosa C. albicansMRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-607 S.epidermidis YIESDPRKFDYIFGAIRDH 814 P. mirabilis E. coli MRSA S.pneumoniae C. jeikeium PF-609 P. mirabilis TEIKLDNNEYLVLNLDDILGILK 815E. coli S. pneumoniae PF-610 S. epidermidis VFLKLKTSKIDLASIIFYP 816 M.luteus P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniaeE. faecalis C. jeikeium C. jejuni PF-612 S. epidermidisGTTLKYGLERQLKIDIHPEITIINLNGGA 817 M. luteus DEFAKL P. mirabilis E. coliP. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeiumPF-613 C. jeikeium ADEFAKL 818 PF-614 S. epidermidis GLDIYA 819 E. coliC. jeikeium PF-615 S. epidermidis FLNRFIFYIFTVKTKSALIKNLFLD 820 M.luteus P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniaeC. jeikeium C. jejuni PF-616 C. jeikeium IVFVVTKEKK 821 PF-617 P.aeruginosa PMNAAEPE 822 C. albicans PF-619 S. epidermidisWSRVPGHSDTGWKVWHRW 823 M. luteus B. subtilis P. mirabilis E. coli P.aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-621S. epidermidis PPSSFLV 824 C. albicans PF-622 S. epidermidisTREDVFSVRLINNIVNKQA 825 P. aeruginosa C. albicans S. pneumoniae E.faecalis C. jeikeium PF-623 S. epidermidis VLFAVYLGALDWLFSWLTQKM 826 P.aeruginosa MRSA S. pneumoniae E. faecalis C. jeikeium PF-625 S.epidermidis SDSTNNARTRKKARDVTTKDIDK 827 M. luteus S. pneumoniae C.jeikeium PF-626 S. epidermidis KYDFDDFEPEEA 828 M. luteus E. coli C.albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-627 S.epidermidis INDLLSYFTLHEK 829 P. aeruginosa MRSA S. pneumoniae E.faecalis C. jeikeium PF-629 S. epidermidis GLAAIATVFALY 830 P.aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-630S. epidermidis IPATPIIHS 831 M. luteus P. mirabilis P. aeruginosa C.albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-631 S.epidermidis LIIYFSKTGNTARATRQI 832 P. aeruginosa C. albicans MRSA S.pneumoniae E. faecalis C. jeikeium PF-632 S. epidermidisTTIQGVASLEKHGFRYTIIYPTRI 833 P. aeruginosa C. albicans MRSA S.pneumoniae E. faecalis C. jeikeium PF-634 S. epidermidisMPKARPVNHNKKKSKITIKSNFTLFYM 834 M. luteus FNP P. mirabilis E. coli P.aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-635S. epidermidis MNAHGHSLIFQKMIVHAFAFFSKQKNY 835 P. aeruginosa LYF C.albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-636 S.epidermidis LVRLA 836 C. albicans MRSA S. pneumoniae E. faecalis PF-637S. epidermidis SRIKQDARSVRKYDRIGIFFYSFKSA 837 P. aeruginosa C. albicansMRSA S. pneumoniae E. faecalis C. jeikeium PF-638 S. epidermidis TFILPK838 C. albicans MRSA C. jeikeium PF-639 S. pneumoniae QATQIKSWIDRLLVSED839 C. jeikeium PF-640 C. albicans MGDINRNF 840 PF-641 S. epidermidisSWKCHHLAIGGSWKCHHLAI 841 M. luteus E. coli C. albicans MRSA E. faecalisC. jeikeium C. jejuni PF-642 M. luteus FTTPMIGIPAGLLGGSYYLKRREEKGK 842MRSA C. jeikeium PF-643 Mycobacteria spp VRCRL 843 PF-644 Mycobacteriaspp TSGLIIGENGLNGL 844 PF-645 Mycobacteria spp SNSVQQG 845 PF-646Mycobacteria spp APASPGRRPG 846 PF-647 Mycobacteria spp GTFLGQKCAAATAS847 PF-648 S. mutans ARRYPAAGS 848 E. coli PF-649 Mycobacteria sppCPRYPFVDVGPAGPWRARWRVGS 849 PF-650 Mycobacteria sppIRSDQPGRQSRSSPRWPTGAGRHR 850 PF-651 Mycobacteria spp PRWPTGAGRHR 851PF-652 Mycobacteria spp FLAPARPDLQAQRQALAQ 852 PF-653 Mycobacteria sppQSVHPLPAETPVADVI 853 PF-654 Mycobacteria spp LSGRLAGRR 854 PF-655 M.smegmatis DAPCFDDQFGDLKCQMC 855 PF-656 Mycobacteria spp RGMFVPFHDVDCVQ856 PF-657 Mycobacteria spp YVANYTITQFGRDFDDRLAVAIHFA 857 PF-658Mycobacteria spp PTTPPPTTPPEIPTGGTVIST 858 PF-659 Mycobacteria spp TVIST859 PF-660 Mycobacteria spp TDPQATAAPRRRTSPR 860 PF-661 Mycobacteria sppPDEDIRRRAILPPAGPCRPMSPE 861 PF-662 Mycobacteria sppGKQSRAHGPVASRREFRRKSG 862 PF-663 Mycobacteria spp ATLIPRKA 863 PF-664 M.smegmatis DQLCVEYPARVSTG 864 PF-665 Mycobacteria spp VLRVATAVGEVPTGL 865PF-666 Mycobacteria spp PNRRSRPR 866 PF-667 Mycobacteria sppPAHQRLRIDQRLVADRDMVQDYES 867 PF-668 Mycobacteria sppTNAESMALAFRGRVHMSVNIAGLT 868 PF-669 Mycobacteria sppRADRIESYPADGDRVITLWRNPYR 869 PF670 Mycobacteria spp TVIVAPMHSGV 870PF-671 S. mutans TVSAFRTVH 871 E. coli PF-673 S. mutans VRRLRM 872 E.coli PF-674 S. mutans DGCDSEPALTYR 873 E. coli PF-675 Mycobacteria sppEIIPISPTRRCEMHTMSSAEYRGL 874 PF-676 S. mutans AEYRGL 875 E. coli PF-677Mycobacteria spp TCRGAGMH 876 PF-678 Mycobacteria sppRDRRWTRRDMYDWLESARV 877 PF-679 S. mutans CRARFIRR 878 E. coli PF-680Mycobacteria spp ADPHPTTGI 879 PF-681 M. smegmatisTALTTVGVSGARLITYCVGVEDI 880 PF-682 Mycobacteria spp RRGKSEQGLSRR 881PF-683 Mycobacteria spp LWPVA 882 PF-684 Mycobacteria sppRKLSLASGFALWRRSLV 883 PF-685 Mycobacteria spp PTLWLACL 884 PF-686 M.smegmatis LAVLMGYIGYRGWSGKRHINRQ 885 PF-687 Mycobacteria sppAKRVLSLAVAPHRRQPVQGT 886 PF-688 Mycobacteria spp ARNHAVIPAG 887 PF-689S. mutans SAPSG 888 E. coli PF-690 Mycobacteria sppMIPLAGDPVSSHRTVEFGVLGTYLVSG 889 GSL PF-691 Mycobacteria sppHRTVEFGVLGTYLVSGGSL 890 PF-692 Mycobacteria spp GVAREDPLEPDPLAPIIDDSR891 PF-693 Mycobacteria spp PDPAR 892 PF-694 Mycobacteria sppDLIRPLYSMSAPSVA 893 PF-695 Mycobacteria spp ALSVMLGNIPLVVPNANQL 894PF-696 Mycobacteria spp IRSGISAAYARPLR 895 PF-697 Mycobacteria sppRADARAK 896 PF-698 Mycobacteria spp SSGRAGVKCRRPTGR 897 PF-699Mycobacteria spp GRAGVKCRRPTGR 898 PF-700 Mycobacteria spp LNWPFTGR 899PF-701 S. mutans PRGAQSGHG 900 PF-702 Mycobacteria spp LSGRLAGRR 901PF-703 Mycobacteria spp MTTVDNIVGLVIAVALMAFLFAALLFPE 902 KF PF-704Mycobacteria spp APAARAAL 903 PF-705 S. mutans GEEEGTVAD 904 E. coliPF-706 L. pneumophila LGYGAWIGCGLGLNGFHRID 905 PF-707 S. mutansIDPESIVTTNNKQDNVDEQ 906 E. coli PF-709 S. mutans NKKHSPMD 907 PF-711 S.mutans KTAGPTGTIYKTN 908 PF-712 S. mutans QIYRHVHKVQAKSANLRLY 909 E.coli PF-714 L. pneumophila FVVTQRMLRMYKK 910 PF-716 S. mutansHGENHHHKSDEKDNDSSEKKD 911 PF-717 E. coli PQSEVTFENIYAPKANGGGLYGI 912PF-720 S. mutans SLDMGK 913 PF-724 L. pneumophila CYRFLTPKRPTRIS 914PF-727 S. mutans AYARCRHDYPFTLGQMQTH 915 E. coli PF-728 S. mutansAIGQEQDRREYYYYSGYPYYY 916 E. coli PF-731 L. pneumophilaRHKLIRLPLSESVFCFLNNPKI 917 PF-732 E. coli DRPSQTTHHTLSSSRITGPS 918PF-733 S. mutans VISRQMGSEAVLELFIIM 919 E. coli PF-735 S. mutansYDPLFPNDKN 920 E. coli PF-737 S. epidermidis KSSGSSASASSTAGGSSSK 921 S.pneumoniae PF-738 S. epidermidis KSGATSAASGAKSGASS 922 C. albicans C.jeikeium PF-741 S. epidermidis AKREDTVAAQIGANILNLIQ 923 M. luteus P.mirabilis P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalisPF-744 S. epidermidis LGVGTFVGKVLIKNQQKQKSKKKAQ 924 M. luteus E. coliMRSA S. pneumoniae E. faecalis C. jeikeium PF-745 S. epidermidisANSQNSLFSNRSSFKSIFDKKSNITTNAT 925 M. luteus TPNSNIIIN C. albicans PF-746S. epidermidis FLGNSQYFTRK 926 M. luteus E. coli C. albicans S.pneumoniae E. faecalis C. jeikeium PF-748 S. epidermidisFQGFFDVAVNKWWEEHNKAKLWKNV 927 M. luteus KGKFLEGEGEEEDDE E. coli P.aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-749S. epidermidis GVNKWWEEHNKAKLWKNVKGKFLEG 928 M. luteus EGEEEDDE E. coliP. aeruginosa C. albicans S. pneumoniae C. jeikeium PF-750 M. luteusAESSPAKTTA 929 C. jeikeium PF-751 S. epidermidis AESSPAQETT 930 E. coliC. albicans C. jeikeium PF-752 S. epidermidisLHVIRPRPELSELKFPITKILKVNKQGLKK 931 E. coli MRSA S. pneumoniae E.faecalis PF-756 S. epidermidis DALLRLA 932 M. luteus C. albicans MRSA C.jeikeium PF-757 M. luteus PQAISSVQQNA 933 C. albicans MRSA PF-758 S.epidermidis PEIIKIVSGLL 934 M. luteus E. coli MRSA S. pneumoniae E.faecalis C. jeikeium PF-760 S. epidermidis DHITLDDYEIHDGFNFELYYG 935 M.luteus PF-761 S. epidermidis SKFELVNYASGCSCGADCKCASETECK 936 M. luteusCASKK P. mirabilis P. aeruginosa C. albicans MRSA S. pneumoniae E.faecalis PF-762 M. luteus PAPAPSAPAPAPEQPEQPA 937 C. albicans PF-763 S.epidermidis GIWMARNYFHRSSIRKVYVESDKEYER 938 M. luteus VHPMQKIQYEGNYKSQE. coli C. albicans MRSA S. pneumoniae E. faecalis PF-764 S. epidermidisGYFEPGKRD 939 M. luteus C. albicans MRSA S. pneumoniae E. faecalis C.jeikeium PF-765 S. epidermidis YLYWEVEHKPIIAKRDAYYAQLRKQKE 940 M. luteusIEEGA E. coli MRSA E. faecalis C. jeikeium PF-766 S. epidermidisDAYYAQLRKQKEIEEGA 941 M. luteus C. albicans MRSA E. faecalis C. jeikeiumPF-767 S. epidermidis DGKQGEPVALKPTDN 942 M. luteus E. coli MRSA S.pneumoniae E. faecalis C. jeikeium PF-768 S. epidermidis GFRGGKRGGARG943 S. pneumoniae E. faecalis C. jeikeium PF-770 S. epidermidisGVGIGFIMMGVVGYAVKLVHIPIRYLIV 944 M. luteus P. mirabilis E. coli P.aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-772S. epidermidis TKESSS 945 C. albicans MRSA S. pneumoniae C. jeikeiumPF-773 S. epidermidis TLKESK 946 C. albicans C. jeikeium PF-776 S.epidermidis VSILLYLSATIILPNVLRLLVARAIIVRV 947 M. luteus P. mirabilis C.albicans MRSA S. pneumoniae E. faecalis PF-777 Mycobacteria spp.PGADGKLAEASAAIARLVRS 948 PF-778 Mycobacteria spp. MNLILTAHGT 949 PF-779Mycobacteria spp. IYGDFFNFYLCDISLKVNGLQPGGPVRT 950 VKLFGQPTGRCTPQ PF-780Mycobacteria spp. AVYDALVALAAAEHRAELATRDARAK 951 DTYEKIGVHVVVAA PF-781Mycobacteria spp. PLVVVNHRRAERSRG 952 PF-782 Mycobacteria spp.TGPRRGIDLTSNRALSEVLDEGLELNSRK 953 PF-783 Mycobacteria spp.FTSEVRGVFTYRVNKAGLITNMRGYW 954 NLDMMTFGNQE PF-784 Mycobacteria spp.MAMTTVDNIVGLVIAVALMAFLFAALL 955 FPEKF PF-785 Mycobacteria spp.MRPQHSPAGKAFVVKKITHEQS 956 PF-786 Mycobacteria spp. LSERERRRLKRGII 957PF-787 Mycobacteria spp. MTERQRRALLKQHPEVVSWSDYLEKR 958 KRRTGTAG PF-788Mycobacteria spp. GLITVFAGTARILQLRRAAKKTHAAALR 959 PF-789 Mycobacteriaspp. PRGAQSGHG 960 PF-790 Mycobacteria spp. PAGPDHLDQRDHR 961 PF-791 S.mutans IFLTTQNTDYSEHNAA 962 PF-792 S. mutans ALHASGIQAI 963 PF-793 S.mutans YTQUNNASAYAMLLTNKDTVP 964 PF-794 S. mutans NLYFENQGN 965 PF-795S. mutans ALHKSGIQVIADWVPDQIYN 966 PF-796 S. mutans YTQSNIPTAYALMLSNKDSI967 PF-797 S. mutans WYYFDNNGYM 968 PF-798 S. mutansALHSKGIKVMADWVPDQMYA 969 PF-799 S. mutans YTHYNTALSYALLLTNKSSVP 970PF-800 S. mutans WYYFDNNGYM 971 PF-C003 A. naeslundiiFCSVDHDVITIAADHVKQGAEA 972 P. gingivalis S. mutans PF-C008 A. naeslundiiAQPRRTWLVNFGEVPSPGLTNDGMPDH 973 PF-C034 S. mutans HPMPITVRSRKPGPLTAPSEH974 E. coli PF-C045 A. naeslundii FREGMGWPLSNEGSPTAPLPKHRNQV 975 T.denticola PF-C050 A. naeslundii QGLARPVLRRIPL 976 S. mutans PF-C052 A.naeslundii SRFRNGV 977 F. nucleatum S. mutans PF-C055 A. naeslundiiYNLSIYIYFLHTITIAGLITLPFII 978 F. nucleatum P. gingivalis S. mutansPF-C057 A. naeslundii YFWWYWVQDCIPYKNNEVWLELSNN 979 F. nucleatum MK P.gingivalis S. mutans PF-C058 A. naeslundii FETGFGDGYYMSLWGLNEKDEVCKVV980 F. nucleatum IPFINPELID P. gingivalis S. mutans PF-C061 A.naeslundii TLNYKKMFFSVIFLLGLNYLICNSPLFFK 981 F. nucleatum QIEF P.gingivalis S. mutans T. denticola PF-C062 A. naeslundiiPLARATEVVATLFIICSLLLYLTR 982 F. nucleatum P. gingivalis S. mutans T.denticola PF-C063 A. naeslundii SHFRKGD 983 F. nucleatum S. mutansPF-C064 A. naeslundii DEEALEMGANLYAQFAIDFLNSKK 984 F. nucleatum P.gingivalis S. mutans T. denticola PF-C065 A. naeslundiiDEERYSDSYFLKEKVFYLILALFLILFHQ 985 F. nucleatum KYLYFLEIITI P. gingivalisS. mutans PF-C068 A. naeslundii LNLFASI 986 F. nucleatum S. mutansPF-C069 A. naeslundii NALMLREMQLAKNIKVEVTDVLSNKK 987 F. nucleatum YC P.gingivalis S. mutans T. denticola PF-C071 A. naeslundii QVIVKIL 988 F.nucleatum S. mutans PF-C072 A. naeslundii KKMFSLIRKVNWIFFILFIVLDLTNVFPLI989 F. nucleatum RTILFAILSRQ P. gingivalis S. mutans T. denticolaPF-C075 A. naeslundii KALVISVFAIVFSIIFVKFFYWRDKK 990 F. nucleatum P.gingivalis S. mutans T. denticola PF-C080 A. naeslundii INIPGLF 991 F.nucleatum S. mutans PF-C084 A. naeslundii FFSVIFLFGLNYLICNSPLFNILR 992F. nucleatum P. gingivalis S. mutans PF-C085 A. naeslundiiKKFKIFVIINWFYHKYIILNFEENF 993 F. nucleatum P. gingivalis S. mutans T.denticola PF-C086 A. naeslundii ELFFTILSDCNELFLLHLLQQPLFYIKKGK 994 F.nucleatum P. gingivalis S. mutans T. denticola PF-C088 A. naeslundiiDIANNILNSVSERLIIA 995 F. nucleatum P. gingivalis S. mutans T. denticolaPF-C091 A. naeslundii ASNTPRFVRLTLFNFYSKIWNVTHLFLF 996 F. nucleatum NNLP. gingivalis S. mutans T. denticola PF-C093 A. naeslundii EKLGTMV 997F. nucleatum S. mutans PF-C095 A. naeslundii LLALNMNEDTYYFELFFIFDNQNKKWL998 F. nucleatum IFDLKERG P. gingivalis S. mutans PF-C098 A. naeslundiiPETKGKVSAFVFGIVVANVIAVVYILYM 999 F. nucleatum LREIGIIQ P. gingivalis S.mutans T. denticola PF-C120 A. naeslundii ASLSTMTFKVMELKELIILLCGLTMLMI1000 F. nucleatum QTEFV P. gingivalis S. mutans T. denticola PF-C131 A.naeslundii QWIVAKREIRMHIYCHISVIHVIIFFG 1001 F. nucleatum P. gingivalisS. mutans PF-C134 A. naeslundii NELMKYPATLTATATTPGIKYSHLCSVCL 1002 F.nucleatum P. gingivalis S. mutans T. denticola PF-C135 A. naeslundiiKNTHAYLRVLRLSSLILSYQASVYPLFA 1003 F. nucleatum YLCQQKDY P. gingivalis S.mutans PF-C136 A. naeslundii LILSYQASVYPLFAYLCQQKDY 1004 F. nucleatum P.gingivalis S. mutans T. denticola PF-C137 A. naeslundiiQRMYWFKRGFETGDFSAGDTFAELK 1005 F. nucleatum P. gingivalis S. mutansPF-C139 A. naeslundii LLASHPERLSLGVFFVYRVLHLLLENT 1006 F. nucleatum P.gingivalis S. mutans T. denticola PF-C142 A. naeslundiiDFPPLSFFRRRFHAYTAPIDNFFGANPF 1007 F. nucleatum P. gingivalis S. mutansT. denticola PF-C143 A. naeslundii VVFGGGDRLV 1008 F. nucleatum P.gingivalis S. mutans T. denticola PF-C145 A. naeslundii YGKESDP 1009 F.nucleatum P. gingivalis S. mutans T. denticola PF-C160 F. nucleatumAASGFTYCASNGVWHPY 1010 PF-C180 F. nucleatum TVEELDKAFTWGAAAALAIGVIAINVG1011 P. gingivalis LAAGYCYNNNDVF S. mutans T. denticola PF-C181 P.gingivalis KMRAGQVVFIYKLILVLLFYVLQKLFD 1012 LKKGCF PF-C194 A. naeslundiiNTNDLLQAFELMGLGMAGVFIVLGILYI 1013 F. nucleatum VAELLIKIFPVNN P.gingivalis S. mutans T. denticola PF-C259 F. nucleatum AEIQPHCLSVL 1014S. mutans PF-C271 A. naeslundii FFPSYYSIIITYF 1015 F. nucleatum P.gingivalis S. mutans T. denticola PF-C273 A. naeslundiiKNMLKRRMKQKRLFDEEDRLRVLSKY 1016 P. gingivalis TKSYY S. mutans T.denticola PF-C281 A. naeslundii KKEKLLTAIRLQHRAEIRGYFTIFFLFFRI 1017 F.nucleatum P. gingivalis S. mutans T. denticola PF-C285 A. naeslundiiFTIIELKKQKIKHGENNKKTAHPLNEPF 1018 F. nucleatum CARA P. gingivalis S.mutans T. denticola PF-C290 A. naeslundii GNVHPESDFHNLIQFIKTFLYFTIFFKYFL1019 F. nucleatum P. gingivalis S. mutans T. denticola PF-C291 A.naeslundii HPFLTGTGCPLFLIFRLFFVKAYFSFTVF 1020 F. nucleatum P. gingivalisS. mutans PF-S003 S. epidermidis ALALLKQDLLNFEGRGRIITSTYLQFNE 1021 M.luteus GCVP P. mirabilis E. coli P. aeruginosa C. albicans MRSA S.pneumoniae E. faecalis C. jeikeium C. jejuni M. smegmatis PF-S004 S.epidermidis VLLNIFRTLLEFFSPSNAPGAEDVPLPDT 1022 MRSA QA C. jeikeiumPF-S007 S. epidermidis VVAGVVLLTALAVGSKRKEKKQIKEIQ 1023 MRSA RLLAATRPF-S015 S. epidermidis IENLERGARRPP 1024 MRSA C. jeikeium PF-S018 S.epidermidis GMPQIPRLRI 1025 M. luteus C. albicans MRSA E. faecalis C.jeikeium C. jejuni PF-S023 S. epidermidis MAEDERRALKRRTNRGRTRTRKRITV1026 MRSA PF-S026 S. epidermidis TELKYNGEEYLLLTQRDILAVIEK 1027 MRSA C.jeikeium PF-S029 M. luteus TSDTQSQSPWLFDNADIVNIYPVQLMHS 1028 P.mirabilis SDND E. coli C. albicans C. jeikeium C. jejuni *Peptidebinding was conducted in aqueous buffers that varied depending onpeptide solubility. For example: Brain Heart Infusion (BHI) Media;1× Phosphate-buffered saline (PBS); 0.05% v/v Tween-20; 0.05% v/vTween-80; 1% v/v Glycerol; 50 μM Guanidine hydrochloride; 0.05% v/vAcetic acid; 50 μM Urea; 1% v/v Polyethylene glycol 400 (PEG 400); 20 mMSodium glutamate; 50 mM Piperazine-1,4-bis(2-ethanesulfonic acid)(PIPES); 50 mM Sodium acetate; 1% v/v Pluronic 17R4; 1% w/v PluronicF108; 1% w/v Pluronic P123; 0.2% v/v Cetyl trimethylammonium bromide(CTAB); 0.8% v/v β-D-Octyl glucoside (BOG); 0.2% CTAB and 0.05%Tween-20; 0.2% CTAB and 0.05% Tween-80; 0.2% CTAB and 1% glycerol; and20 mM HEPES (4-(2-hydroxyethyl)-1- piperazineethanesulfonic acid), 150mM sodium chloride, 1 mM magnesium chloride and 0.1% CTAB. Preferably,binding was evaluated in 1× PBS. **Three-amino acid code: Dab:Diaminobutyric acid; Orn: Ornithine; cDOrn, cOrn: side-chain cyclicalOrnithine; Abreviations: c(X . . . Y) indicates amino acids are cyclic,connected X to Y; DX indicates D-isoform amino acids.

In certain embodiments, the amino acid sequence of the targetingpeptides comprises or consists of a single amino acid sequence, e.g., aslisted above in Table 3. In certain embodiments the amino acid sequenceof the targeting peptides comprises two copies, three copies, fourcopies, five copies six copies or more of one or more of the amino acidsequences listed in Table 3, and/or Table 10, and/or Table 12. Thus,compound targeting constructs are contemplated where the constructcomprises multiple domains each having targeting activity. The targetingdomains comprising such a construct can be the same or different. Incertain embodiments the construct comprises at least 2, at least 3, atleast 4, at least 5, at least 6, at least 7, or at least 8 differenttargeting domains each domain comprising a different targeting sequence.

Various targeting domains comprising such a construct can be joineddirectly to each other or two or more of such domains can be attached toeach other via a linker. An illustrative, but non-limiting, list ofsuitable linkers is provided in Table 16. Thus, in certain embodiments,two or more targeting domains comprising a compound/multiple targetingconstruct are chemically conjugated together.

In certain embodiments the two or more targeting domains comprising theconstruct are joined by a peptide linker. Where all the targetingdomains are attached directly to each other or are joined by peptidelinkers, the entire construct can be provided as a single-chain peptide(fusion protein).

In various embodiments, the targeting peptides described herein compriseone or more of the amino acid sequences shown in Table 3, and/or Table10, and/or Table 12 (and/or the retro, inverso, retroinverso, etc. formsof such sequences). In certain embodiments the peptides range in lengthup to about 100 amino acids in length, preferably up to about 80, about70, about 60, or about 51 amino acids in length. In certain embodimentsthe peptides range in length from about 8 amino acids up to about 100amino acids 80 amino acids, 60 amino acids or about 51 amino acids inlength. In certain embodiments the peptides range in length from about 8up to about 50, 40, 30, 20, 15, 15, 13, or 12 amino acids in length.

As shown in Tables 3, 10, and 12 the various amino acid sequencesdescribed herein target particular microorganisms. The range of activityof the peptides or compositions comprising such peptides can beincreased by including amino acid sequences that target differentmicroorganisms either as separate components and/or as multiple domainswithin a single construct.

In some embodiments greater specificity and/or avidity can be obtainedby including multiple different amino acid sequences that target thesame microorganism.

II. Antimicrobial Peptides.

A) Uses of Antimicrobial Peptides.

The antimicrobial peptides described herein also have a wide variety ofuses. For example, the peptides can be formulated individually, incombination, in combination with other antimicrobial peptides, and/or incombination with various antibacterial agents to provide antimicrobialpharmaceuticals.

In various embodiments, the antimicrobial peptides described herein canbe formulated individually, in combination, in combination with otherantimicrobial peptides, and/or in combination with various antibiotic(e.g., antibacterial) agents in “home healthcare” formulations. Suchformulations include, but are not limited to toothpaste, mouthwash,tooth whitening strips or solutions, contact lens storage, wetting, orcleaning solutions, dental floss, toothpicks, toothbrush bristles, oralsprays, oral lozenges, nasal sprays, aerosolizers for oral and/or nasalapplication, wound dressings (e.g., bandages), and the like.

In various embodiments the antimicrobial peptides described herein canbe formulated individually, in combination, in combination with otherantimicrobial peptides, and/or in combination with various antibiotic(e.g., antibacterial) agents in various cleaning and/or sterilizationformulations for use in agriculture, in fool preparation and transport,in the home, workplace, clinic, or hospital.

In certain embodiments the antimicrobial peptides described herein areattached to one or more targeting moieties to specifically and/or topreferentially deliver the peptide(s) to a target (e.g. a targetmicroorganism, biofilm, bacterial film, particular tissue, etc.).

Other possible uses of the targeting and/or antimicrobial peptidesdisclosed herein include, but are not limited to biofilm dispersal,biofilm retention, biofilm formation, anti-biofilm formation, cellagglutination, induction of motility or change in motility type,chemoattractant or chemorepellent, extracellular signal for sporogenesisor other morphological change, induction or inhibition of virulence geneexpression, utilized as extracellular scaffold, adhesin or binding site,induction or suppression of host immune response, induction orsuppression of bacterial/fungal antimicrobial molecule production,quorum-sensing, induction of swarming behavior, apoptosis or necrosisinducing in eukaryotic cells, affecting control of or inducing theinitiation of cell cycle in eukaryotes, in archaea or prokaryotes,induces autolysis or programmed cell death, inhibition of phage/virusattachment or replication, evasion of innate immunity, induction orinhibition of genetic transformation or transduction competence,induction or inhibition of pilus-mediated conjugation, induction orinhibition of mating behavior in bacteria and fungi, induction orinhibition of nodule formation or metabolic compartmentalization, metal,ion, or nutrient binding, acquisition or inhibition of metal, ion, ornutrient binding and acquisition, and the like.

In certain embodiments, compositions and methods are provided fordecreasing the infectivity, morbidity, and rate of mortality associatedwith a variety of pathogens. The present invention also relates tomethods and compositions for decontaminating areas, samples, solutions,and foodstuffs colonized or otherwise infected by pathogens andmicroorganisms. Certain embodiments of the present compositions arenontoxic and may be safely ingested by humans and other animals.Additionally, certain embodiments of the present invention arechemically stable and non-staining.

In some embodiments, the present invention provides compositions andmethods suitable for treating animals, including humans, exposed topathogens or the threat of pathogens. In some embodiments, the animal iscontacted with effective amounts of the compositions prior to exposureto pathogenic organisms. In other embodiments, the animal or human iscontacted with effective amounts of the compositions after exposure topathogenic organisms. Thus, the present invention contemplates both theprevention and treatment of microbiological and other infections.

In certain embodiments compositions and methods are provided fordecontaminating solutions and surfaces, including organic and inorganicsamples that are exposed to pathogens or suspected of containingpathogens. In still other embodiments of the present invention, thecompositions are used as additives to prevent the growth of harmful orundesired microorganisms in biological and environmental samples.

These applications of the peptides described herein are intended to beillustrative and not limiting. Using the teaching provided herein, otheruses will be recognized by one of skill in the art.

B Illustrative Novel Antimicrobial Peptides.

Antimicrobial peptides (also called host defense peptides) are anevolutionarily conserved component of the innate immune response and arefound among all classes of life. Unmodified, these peptides are potent,broad spectrum antibiotics which demonstrate potential as noveltherapeutic agents. Antimicrobial peptides have been demonstrated tokill Gram-negative and Gram-positive bacteria (including strains thatare resistant to conventional antibiotics), mycobacteria (includingMycobacterium tuberculosis), enveloped viruses, and fungi.

Naturally-occurring antimicrobial peptides are typically short peptides,generally between 12 and 50 amino acids. These peptides often includetwo or more positively charged residues provided by arginine, lysine or,in acidic environments, histidine, and frequently a large proportion(generally >50%) of hydrophobic residues (see, e.g., Papagianni et al.(2003) Biotechnol Adv 21: 465; Sitaram and Nagaraj (2002) Curr Pharm Des8: 727; Dürr et al. (2006) Biochim. Biophys. Acta 1758: 1408-1425).

Frequently the secondary structures of these molecules follow 4 themes,including i) α-helical, ii) β-stranded due to the presence of 2 or moredisulfide bonds, iii) β-hairpin or loop due to the presence of a singledisulfide bond and/or cyclization of the peptide chain, and iv)extended. Many of these peptides are unstructured in free solution, andfold into their final configuration upon partitioning into biologicalmembranes. The ability to associate with membranes is a definitivefeature of antimicrobial peptides although membrane permeabilisation isnot necessary. These peptides have a variety of antimicrobial activitiesranging from membrane permeabilization to action on a range ofcytoplasmic targets.

The modes of action by which antimicrobial peptides kill bacteria isvaried and includes, but is not limited to disrupting membranes,interfering with metabolism, and targeting cytoplasmic components. Inmany cases the exact mechanism of killing is not known.

In certain embodiments the antimicrobial peptides include peptidescomprising or consisting of one or more of the amino acid sequencesshown in Tables 4 (SEQ ID NOs:1029-1078), and/or Table 5 (SEQ IDNOs:1079-1566). In various embodiments the peptides include peptidescomprising or consisting of the retro, inverso, retro-inverso, and/orbeta form of one or more of the amino acid sequences shown in Tables 4(SEQ ID NOs:1029-1078), and/or Table 5 (SEQ ID NOs:1079-1566). Thepeptides can comprise all “L” amino acids, all “D” amino acids, orcombinations of “L” and “D” amino acids. Also contemplated are circularpermutations of these sequences as well as peptides comprising orconsisting of the retro, inverso, retro-inverso, and/or beta form ofsuch circular permutations.

It will also be recognized, that in certain embodiments, any peptide orcompound AMP described herein can be circularized.

In various embodiments the peptides can optionally bear one or moreprotecting groups, e.g., and the amino and/or carboxyl termini, and/oron side chains.

Also contemplated are peptides comprising one, two, three four, or fiveconservative substitutions of these amino acid sequences.

TABLE 4 Novel antimicrobial peptides, target microorganisms and MICvalues. Organism MIC SEQ ID (μM) Structure/sequence ID NO K-1 S. mutans,25 GLGRVIGRLIKQIIWRR 1029 K-2 S. mutans, 12.5 VYRKRKSILKIYAKLKGWH 1030K-7 S. mutans, 12.5 NYRLVNAIFSKIFKKKFIKF 1031 K-8 S. mutans, 4KILKFLFKKVF 1032 K-9 S. mutans, 4 FIRKFLKKWLL 1033 K-10 S. mutans, 4KLFKFLRKHLL 1034 K-11 S. mutans, 4 KILKFLFKQVF 1035 K-12 S. mutans, 8KILKKLFKFVF 1036 K-13 S. mutans, 16 GILKKLFTKVF 1037 K-14 S. mutans, 8LRKFLHKLF 1038 K-15 S. mutans, 4 LRKNLRWLF 1039 K-16 S. mutans, 8FIRKFLQKLHL 1040 P. aeruginosa, 12.5 MRSA, 25 K-17 S. mutans, 8FTRKFLKFLHL 1041 K-18 S. mutans, 16 KKFKKFKVLKIL 1042 K-19 S. mutans, 16LLKLLKLKKLKF 1043 K-20 S. mutans, 8 FLKFLKKFFKKLKY 1044 K-21 S. mutans,8 GWLKMFKKIIGKFGKF 1045 K-22 S. mutans, 8 GIFKKFVKILYKVQKL 1046 1T-88GRLVLEITADEVKALGEALANAKI 1047 PF-531 A. baumannii, 25YIQFHLNQQPRPKVKKIKIFL-NH2 1048 P. aeruginosa, 50 T. rubrum, 50 A. niger,25 B. subtilis, 25 C. difficile, 12.5 C. jeikeium, 6.25 S. epidermidis,50 S. mutans, 12.5 PF-527 P. aeruginosa, 50 GSVIKKRRKRMAKKKHRKLLKKTRIQR1049 T. rubrum, 25 RRAGK A. niger, 50 B. subtilis, 12.5 C. jeikeium,6.25 MRSA, 50 S. epidermidis, 25 PF-672 C. albicans, 1.56MRFGSLALVAYDSAIKHSWPRPSSVRR 1050 T. rubrum, 0.78 LRM A. niger, 3 B.subtilis, 0.78 E. faecalis, 3.13 MRSA, 1.56 S. epidermidis, 0.39 PF-606E. coli, 50 FESKILNASKELDKEKKVNTALSFNSHQ 1051 MRSA, 50 DFAKAYQNGKI S.epidermidis, 50 S. mutans, 50 S. pneumoniae, 50 PF-547 T. rubrum, 25WSRVPGHSDTGWKVWHRW-NH2 1052 B. subtilis, 25 S. mutans, 12.5 PF-006 A.baumannii, 50 MGIIAGIIKFIKGLIEKFTGK 1053 B. subtilis, 25 MRSA, 50 PF-545A. niger, 50 RESKLIAMADMIRRRI-NH2 1054 B. subtilis, 25 MRSA, 50 PF-278C. albicans, 50 LSLATFAKIFMTRSNWSLKRFNRL 1055 T. rubrum, 50 S.epidermidis, 50 PF-283 T. rubrum, 50 MIRIRSPTKKKLNRNSISDWKSNTSGRF 1056B. subtilis, 50 FY S. epidermidis, 50 PF-307 C. albicans, 50MKRRRCNWCGKLFYLEEKSKEAYCCK 1057 T. rubrum, 50 ECRKKAKKVKK B. subtilis,50 PF-168 T. rubrum, 50 VLPFPAIPLSRRRACVAAPRPRSRQRAS 1058 A. niger, 50MRSA, 50 PF-538 A. baumannii, 25 KNKKQTDILEKVKEILDKKKKTKSVGQ 1059 C.difficile, 25 KLY PF-448 A. niger, 25 SLQSQLGPCLHDQRH 1060 S.pneumoniae, 50 PF-583 MRSA, 50 KFQGEFTNIGQSYIVSASHMSTSLNTGK 1061 S.epidermidis, 50 PF-600 E. coli, 50 TKKIELKRFVDAFVKKSYENYILERELK 1062 S.pneumoniae, 50 KLIKAINEELPTK PF-525 A. niger, 50 KFSDQIDKGQDALKDKLGDL1063 S. pneumoniae, 50 PF-529 A. niger, 50 LSEMERRRLRKRA-NH2 1064 S.pneumoniae, 50 PF-148 A. niger, 50 RRGCTERLRRMARRNAWDLYAEHFY 1065 B.subtilis, 50 PF-530 A. baumannii, 25 SKFKVLRKIIIKEYKGELMLSIQKQR 1066PF-522 C. difficile, 25 FELVDWLETNLGKILKSKSA-NH2 1067 PF-497 B.subtilis, 50 LVLRICTDLFTFIKWTIKQRKS 1068 PF-499 B. subtilis, 50VYSFLYVLVIVRKLLSMKKRIERL 1069 PF-322 B. subtilis, 50 GIVLIGLKLIPLLANVLR1070 PF-511 S. pneumoniae, 50 VMQSLYVKPPLILVTKLAQQN 1071 PF-512 S.pneumoniae, 50 SFMPEIQKNTIPTQMK 1072 PF-520 S. pneumoniae, 50LGLTAGVAYAAQPTNQPTNQPTNQPTN 1073 QPTNQPTNQPRW-NH2 PF-521 S. pneumoniae,50 CGKLLEQKNFFLKTR 1074 PF-523 S. pneumoniae, 50ASKQASKQASKQASKQASKQASRSLKN 1075 HLL PF-524 S. pneumoniae, 50PDAPRTCYHKPILAALSRIVVTDR 1076 PF-209 MRSA, 50 NYAVVSHT 1077 PF-437 S.pneumoniae, 50 FQKPFTGEEVEDFQDDDEIPTII 1078Where protecting groups are shown (e.g., —NH₂) they are optional.Conversely any peptide shown without protecting groups can bear one ormore such groups.

In certain embodiments peptides that induce alterations in phenotype orother biological activities can also be used as antimicrobial effectormoieties. Illustrative alternative peptides are shown in Table 5.

TABLE 5 Illustrative list of novel morphology, biofilm and growthdisrupting peptides. SEQ ID ID Organism, effect Structure/sequence NOG-1 S. mutans: Ca2+ DSSQSDSDSDSNSSNTNSNSSITNG 1079 binding G-2 S.mutans: biofilm LPGTLHIQAEFPVQLEAGSLIQIFD 1080 structure G-4 S. mutans:EIPIQLANDLANYYDISLDSIFFW 1081 Biofilm structure G-5 M. xanthus:RDMTVAGKRPNFLIITTDEE 1082 Altered cell morphology G-6 M. xanthus:NTSIVCAVTFAPIKEVPLLWRAGLTLRS 1083 Altered cell RQS morphology G-7 M.xanthus: QAKVEREVERDLVYTLRRLCDPSGSER 1084 Altered cell TK morphology G-8S. mutans: PRMIDIISFHGCHGDHQVWTDPQATAL 1085 Altered biofilm PR structurePF-001 S. epidermidis (C) MNNWIIVAQLSVTVINEIIDIMKEKQKG 1086 M. luteus(C) GK MRSA (R) C. jeikeium (D) PF-002 B. subtilis (R) NDDAQ 1087 S.pneumoniae (H) PF-003 S. epidermidis (D) MNNWIKVAQISVTVINEVIDIMKEKQN1088 M. luteus (A) GGK MRSA (R) C. jeikeium (A) PF-004 S. epidermidis(A) ARLSKAIIIAVIVVYHLDVRGLF 1089 M. luteus (A) MRSA (R) C. jeikeium (A)PF-005 B. subtilis (C) MESIFKIKLMNGICRSENMNMKKKNK 1090 S. pneumoniae (H)GEKI PF-006 S. epidermidis (D) MGIIAGIIKFIKGLIEKFTGK 1091 M. luteus (A)B. subtilis (I) MRSA (I) S. pneumoniae (R) C. jejuni (D) PF-007 S.epidermidis (A) MGIIAGIIKVIKSLIEQFTGK 1092 M. luteus (A) E. coli (A)MRSA (R) E. faecalis (A) PF-008 B. subtilis (D)MIEIGSIAYLNGGSKKYNHILNQENR 1093 C. jejuni (R) PF-009 S. epidermidis (S)SKKYNHILNQENR 1094 PF-010 S. epidermidis (S) MDIDVNKLLQAFVYFKSFEKLRHNNS1095 M. luteus (A) MRSA (R) C. jeikeium (A) PF-011 MRSA (R)MFCYYKQHKGDNFSIEEVKNIIADNEM 1096 C. jeikeium (C) KVN PF-012 S.epidermidis (S) WRGPNTEAGGKSANNIVQVGGAPT 1097 M. luteus (C) MRSA (R) C.jeikeium (A) PF-013 S. epidermidis (C) LIQKGLNQTFIVVIRLNNFIKKS 1098 M.luteus (D) MRSA (R) C. jeikeium (D) PF-015 MRSA (W) SIDKRNLYNLKYYE 1099PF-017 MRSA (M) ESIIE 1100 PF-019 MRSA (M) NDTNK 1101 PF-020 S. mutans(F) MKIILLLFLIFGFIVVVTLKSEHQLTLFSI 1102 S. epidermidis (C) M. luteus (C)MRSA (C) S. pneumoniae (D) PF-021 S. epidermidis (A) FSLNFSKQKYVTVN 1103M. luteus (A) MRSA (R) C. jeikeium (R) PF-022 S. epidermidis (D)MINELKNKNSGIMNNYVVTKESKL 1104 M. luteus (A) MRSA (R) C. jeikeium (A)PF-023 MRSA (S) MTKNTIISLENEKTQINDSENESSDLRK 1105 AK PF-024 S.epidermidis (D) DLRKAK 1106 MRSA (M) PF-025 S. epidermidis (S)LLIIFRLWLELKWKNKK 1107 M. luteus (A) MRSA (R) C. jeikeium (A) PF-026MRSA (M) SIHFIN 1108 PF-027 S. epidermidis (D) HNARKYLEFISQKIDGDKLTKEDSL1109 MRSA (M) PF-028 S. epidermidis (M) ALDCSEQSVILWYETILDKIVGVIK 1110MRSA (R) C. jeikeium (M) PF-029 MRSA (M) NSTNE 1111 PF-030 S.epidermidis (D) MTCHQAPTTTHQSNMA 1112 M. luteus (C) MRSA (R) C. jeikeium(C) PF-031 MRSA (M) MPHHSTTSSRIVVPAHQSNMASTPNLSI 1113 TP PF-032 S.epidermidis (S) RIVVPAHQSNMASTPNLSITP 1114 C. jeikeium (C) PF-033 S.epidermidis (M) MFIFKTTSKSHFHNNVKSLECIKIPINK 1115 B. subtilis (C) NRMRSA (M) S. pneumoniae (R) C. jeikeium (D) C. jejuni (R) PF-034 S.epidermidis (A) EPKKKHFPKMESASSEP 1116 PF-035 MRSA (M) SFYESY 1117PF-036 S. epidermidis (S) ILNRLSRIVSNEVTSLIYSLK 1118 M. luteus (A) MRSA(R) C. jeikeium (A) PF-037 S. epidermidis (D) MTKKRRYDTTEFGLAHSMTAKITLHQ1119 M. luteus (C) ALYK MRSA (R) C. jeikeium (D) PF-040 S. mutans (F)MIHLTKQNTMEALHFIKQFYDMFFILN 1120 S. epidermidis (D) FNV M. luteus (D) B.subtilis (D) P. mirabilis (C) E. coli (C) MRSA (D) S. pneumoniae (D) C.jeikeium (D) C. jejuni (D) PF-041 S. epidermidis (R) ELLVILPGFI 1121MRSA (M) PF-042 S. epidermidis (D) LLLSYFRYTGALLQSLF 1122 M. luteus (C)MRSA (R) C. jeikeium (S) PF-043 S. epidermidis (D)MIKNETAYQMNELLVIRSAYAK 1123 M. luteus (C) MRSA (R) C. jeikeium (A)PF-045 MRSA (S) LDINDYRSTY 1124 PF-046 S. epidermidis (C) LDFYLTKHLTLML1125 MRSA (R) C. jeikeium (R) PF-048 S. epidermidis (D)LYFAFKKYQERVNQAPNIEY 1126 MRSA (W) C. jeikeium (S) PF-049 MRSA (S)AYYLKRREEKGK 1127 PF-051 S. mutans (D) RFFNFEIKKSTKVDYVFAHVDLSDV 1128 S.epidermidis (D) M. luteus (C) MRSA (D) S. pneumoniae (D) PF-052 S.epidermidis (S) QELINEAVNLLVKSK 1129 M. luteus (A) MRSA (R) C. jeikeium(D) PF-053 S. epidermidis (C) KLFGQWGPELGSIYILPALIGSIILIAIVT 1130 M.luteus (D) LILRAMRK B. subtilis (H) E. coli (A) P. aeruginosa (A) C.albicans (A) MRSA (D) S. pneumoniae (S) E. faecalis (A) C. jeikeium (D)C. jejuni (D) PF-056 S. epidermidis (D) AEQLFGKQKQRGVDLFLNRLTIILSILF1131 M. luteus (D) FVLMICISYLGM B. subtilis (C) C. albicans (B) MRSA (M)S. pneumoniae (D) C. jeikeium (S) C. jejuni (D) PF-057 S. epidermidis(D) TMIVISIPRFEEYMKARHKKWM 1132 M. luteus (C) E. coli (M) C. albicans(A) MRSA (M) S. pneumoniae (R) E. faecalis (A) C. jeikeium (A) C. jejuni(D) PF-058 MRSA (M) FADQSQDNA 1133 PF-059 C. jejuni (C)TITLKAGIERALHEEVPGVIEVEQVF 1134 PF-061 S. epidermidis (R)GYNSYKAVQDVKTHSEEQRVTAKK 1135 B. subtilis (R) S. pneumoniae (R) C.jejuni (R) PF-063 S. epidermidis (R) IAAIIVLVLFQKGLLQIFNWILIQLQ 1136 M.luteus (R) B. subtilis (C) P. aeruginosa (A) MRSA (M) S. pneumoniae (D)C. jeikeium (D) C. jejuni (D) PF-064 S. epidermidis (D) DYYGKE 1137 MRSA(M) PF-065 S. epidermidis (D) LEKNTRDNYFIHAIDRIYINTSKGLFPES 1138 MRSA(R) ELVAWG C. jeikeium (A) PF-066 MRSA (S) IKGTVKAVDETTVVITVNGHGTELTFE1139 KPAIKQVDPS PF-067 S. epidermidis (D) DLIVKVHICFVVKTASGYCYLNKREAQ1140 M. luteus (R) AAI B. subtilis (C) P. aeruginosa (A) MRSA (M) S.pneumoniae (D) C. jeikeium (D) C. jejuni (D) PF-068 S. epidermidis (M)SHLINNFGLSVINPSTPICLNFSPVFNLL 1141 M. luteus (D) TVYGITCN B. subtilis(A) E. coli (A) MRSA (M) S. pneumoniae (D) E. faecalis (A) C. jeikeium(R) C. jejuni (D) PF-069 B. subtilis (D) FDPVPLKKDKSASKHSHKHNH 1142 C.jejuni (R) PF-070 B. subtilis (D) SMVKSEIVDLLNGEDNDD 1143 PF-071 S.epidermidis (R) HCVIGNVVDIANLLKRRAVYRDIADVI 1144 M. luteus (R) KMR B.subtilis (D) C. albicans (B) MRSA (C) S. pneumoniae (A) C. jejuni (A)PF-073 S. epidermidis (R) CPSVTMDACALLQKFDFCNNISHFRHF 1145 M. luteus (R)FAIKQPIER MRSA (M) S. pneumoniae (D) C. jeikeium (D) C. jejuni (D)PF-074 S. epidermidis (D) RDIHPIYFMTKD 1146 MRSA (M) PF-075 S.epidermidis (D) FVNSLIMKDLSDNDMRFKYEYYNREK 1147 M. luteus (A) DT MRSA(R) C. jeikeium (D) PF-076 S. epidermidis (S)LYQYELLSKEEYLKCTLIINQRRNEQK 1148 M. luteus (A) MRSA (R) C. jeikeium (A)PF-099 S. epidermidis (D) EIIAYLEGRFANA 1149 C. jeikeium (C) PF-123 S.epidermidis (M) TTRPQVAEDRQLDDALKETFPASDPISP 1150 PF-124 S. epidermidis(C) MADGQIAAIAKLHGVPVATRNIRHFQS 1151 C. jeikeium (R) FGVELINPWSG PF-125S. epidermidis (D) YVVGALVILAVAGLIYSMLRKA 1152 M. luteus (C) PF-127 S.epidermidis (M) MLRYLSLFAVGLATGYAWGWIDGLA 1153 M. luteus (A) ASLAV C.jeikeium (A) PF-128 S. epidermidis (D) GIKVVAARFEEIQFSENFDSIILA 1154 P.aeruginosa (C) PF-129 S. epidermidis (M) MKLLARDPWVCAWNDIW 1155 C.jeikeium (R) PF-133 C. jeikeium (R) GDPTAGQKPVECP 1156 PF-135 C.jeikeium (R) PPARPARIPQTPTLHGASLFRQRS 1157 PF-137 S. epidermidis (D)VLGKGHDLLDVGKTALKSRVFAWLG 1158 M. luteus (D) GS C. jeikeium (A) PF-139S. epidermidis (M) ALSKPAIQARTLCRRQDPP 1159 M. luteus (C) C. jeikeium(R) PF-140 S. epidermidis (D) FHRRVIRASEWALTTRSFSTPLRSAAR 1160 M. luteus(R) P. aeruginosa (A) C. albicans (B) MRSA (M) S. pneumoniae (D) C.jeikeium (D) C. jejuni (D) PF-143 P. aeruginosa (C)LSPRPIIVSRRSRADNNNDWSR 1161 PF-144 S. pneumoniae (H) RSGQPVGRPSRRAWLR1162 PF-145 S. epidermidis (D) GIVLTGRAGLVSGACSMALGVGLG 1163 M. luteus(A) B. subtilis (C) MRSA (M) S. pneumoniae (R) C. jeikeium (R) C. jejuni(R) PF-148 S. epidermidis (D) RRGCTERLRRMARRNAWDLYAEHFY 1164 M. luteus(A) B. subtilis (I) C. albicans (B) MRSA (C) S. pneumoniae (R) C.jeikeium (H) C. jejuni (H) PF-149 MRSA (H) GKVSVLTRVPRSLGGAPANQ 1165PF-153 S. epidermidis (M) GILARADCSQIA 1166 C. jeikeium (C) PF-156 MRSA(H) LITAEQPATAPIAGK 1167 PF-157 S. epidermidis (M)HTAVVWLAGVSGCVALSHCEPA 1168 PF-164 C. jeikeium (R) EEVSRALAGIGLGLGCRIG1169 PF-168 P. aeruginosa (H) VLPFPAIPLSRRRACVAAPRPRSRQRAS 1170 MRSA (I)PF-171 S. epidermidis (R) TQVTLCRTW 1171 M. luteus (R) B. subtilis (D)MRSA (M) S. pneumoniae (D) C. jejuni (R) PF-173 S. epidermidis (A)AGRTAIVQGGG 1172 C. jeikeium (D) PF-175 M. luteus (S)RRRPAGQRPEKASQAMIAA 1173 B. subtilis (D) C. albicans (B) S. pneumoniae(A) C. jejuni (M) PF-176 S. epidermidis (C) RLTSNQFLTRITPFVFAQH 1174 M.luteus (C) C. jeikeium (D) PF-178 S. epidermidis (D) EVYSSPTNNVAITVQNN1175 E. coli (C) MRSA (M) S. pneumoniae (D) PF-180 S. epidermidis (C)SGLGDLGFSSEAK 1176 PF-186 S. epidermidis (C) DADKNLSLERDRFAWRVAAP 1177C. jeikeium (A) PF-188 C. jeikeium (H) ARTFAGRLGTRYFGGLMRSTKA 1178PF-190 S. epidermidis (C) HFILRKPLLFMIHSLKTGPLDRF 1179 C. jeikeium (R)PF-191 S. epidermidis (A) QFCNFAWLFLASNNAQVSALA 1180 MRSA (H) C.jeikeium (R) PF-192 S. epidermidis (D) VEEDEAPPPHY 1181 PF-196 S.epidermidis (C) TTARYIRRQCHTSITPLSQG 1182 C. jeikeium (R) PF-199 S.epidermidis (C) FPAFSFGAIAGSVSVAR 1183 M. luteus (A) C. jeikeium (R)PF-203 S. epidermidis (A) SWKCHHLAI 1184 C. jeikeium (R) PF-204 S.epidermidis (C) ALQKQDMNLPSVKNQLVFLKSTG 1185 M. luteus (C) P. aeruginosa(H) C. jeikeium (D) PF-208 S. epidermidis (D) DAYHCHLVRSPDAHDLSMRIGFV1186 C. jeikeium (A) PF-209 S. epidermidis (C) NYAVVSHT 1187 P.aeruginosa (H) MRSA (I) PF-212 M. luteus (M) NDSKASN 1188 PF-215 M.luteus (T) ELKITNYNVNTVLYRYYKWGNDLCE 1189 PF-220 S. pneumoniae (H)VDPADDGTRHIRPEDGDPIEIDE 1190 PF-224 M. luteus (T) DYFYITLSQKNTF 1191PF-226 S. epidermidis (C) LMFFSENMDKRDTLSGKFRYFAGSKVI 1192 M. luteus (T)KLMNWLSENGK PF-233 S. epidermidis (C) DANAMARTTIAIVYILALIALTISYSL 1193PF-234 M. luteus (T) RTPYILRS 1194 PF-235 M. luteus (T)GIPFSKPHKRQVNYMKSDVLAYIEQNK 1195 MAHTA PF-249 M. luteus (R) INSRYKISF1196 PF-250 M. luteus (T) SEDIFGRLANEKANGLEELRKIRLKQ 1197 PF-255 M.luteus (M) DHKINESQHNPFRSDSNKQNVDFF 1198 PF-257 M. luteus (R)VWENRKKYLENEIERHNVFLKLGQEVI 1199 KGLNALASRGR PF-264 M. luteus (H)MQSLSNRQSLIASYILMGIFLSFGYPPA 1200 SLSKFFCRLSHL PF-270 M. luteus (H)MYLTPYAWIAVGSIFAFSVTTIKIGDQN 1201 DEKQKSHKNDVHKR PF-271 M. luteus (T)AAQPQTT SP 1202 PF-273 S. epidermidis (C) LVGALLIFVALIYMVLKGNADKN 1203PF-274 M. luteus (M) SIQEAEKIIKNDPFYIHDVADYDFMWF 1204 EPSKSLEEIKEFVPF-276 M. luteus (M) LDLALSTNSLNLEGFSF 1205 PF-278 S. epidermidis (I)LSLATFAKIFMTRSNWSLKRFNRL 1206 M. luteus (R) C. albicans (B) PF-283 S.epidermidis (H) MIRIRSPTKKKLNRNSISDWKSNTSGRF 1207 B. subtilis (H) FYPF-289 B. subtilis (C) MGRHLWNPSYFVATVSENTEEQIRKY 1208 RKNK PF-290 S.epidermidis (C) MVHDMTNGTLIIVKH 1209 PF-292 S. epidermidis (C)SFVSTTVRLIFEESKRYKF 1210 B. subtilis (C) PF-293 S. epidermidis (C) YDPLK1211 PF-294 S. epidermidis (C) DFLVNFLWFKGELNWGKKRYK 1212 PF-296 S.epidermidis (C) GAFGMPSIKTNTICGEKGKFISACDAW 1213 B. subtilis (C) LSNLKPF-297 S. epidermidis (C) ISKGIDDIVYVINKILSIGNIFKIIKRK 1214 B. subtilis(C) PF-301 S. epidermidis (C) GIVLIGLKLIPLLANVLN 1215 B. subtilis (C)PF-303 B. subtilis (C) EYPWSWISEPWPWDKSFYK 1216 PF-305 B. subtilis (C)MREWICPSCNETHDRDINASINILKEGL 1217 RLITIQNK PF-306 B. subtilis (C)GCILPHKKDNYNYIMSKFQDLVKITSKK 1218 PF-307 S. epidermidis (T)MKRRRCNWCGKLFYLEEKSKEAYCC 1219 B. subtilis (H) KECRKKAKKVKK C. albicans(B) PF-310 S. epidermidis (C) GVALIGTILVPLLSGLFG 1220 PF-313 S.epidermidis (C) YITSHKNARAIIKKFERDEILEEVITHYL 1221 NRK PF-318 S.epidermidis (C) MGRHLWNPSYFVATVSENTEEQIRKYI 1222 B. subtilis (C)NNQKKQVK PF-319 S. epidermidis (C) SIGSMIGMYSFRHKTKHIKFTFGIPFILF 1223 B.subtilis (C) LQFLLVYFYILK PF-322 S. epidermidis (C) GIVLIGLKLIPLLANVLR1224 B. subtilis (H) PF-335 S. epidermidis (C) AAYPIEDWSDWYEDFFIMLSNI1225 B. subtilis (C) PF-339 S. epidermidis (C) KKIDILINKYMYLSK 1226 B.subtilis (C) PF-342 S. epidermidis (C) AFSGVYKTLIVYTRRK 1227 B. subtilis(C) PF-344 E. coli (A) DERLPEAKAIRNFNGSVMVLGR 1228 PF-347 S. epidermidis(C) GIFTGVTVVVSLKHC 1229 E. coli (C) MRSA (C) E. faecalis (C) PF-349 S.epidermidis (C) MPKSCHVPVLCDFFFLVIIKFLALFKTI 1230 E. coli (C) QS MRSA(C) E. faecalis (C) PF-350 S. epidermidis (C) LAVILRAIVY 1231 E. coli(C) MRSA (C) PF-354 MRSA (H) FTFSKCRASNGRGFGTLWL 1232 PF-355 S.epidermidis (C) WIAIGLLLYFSLKNQ 1233 E. coli (C) P. aeruginosa (A) MRSA(A) S. pneumoniae (D) E. faecalis (D) C. jejuni (D) PF-356 S.epidermidis (S) VSIKIGAIVIGMIGLMELLTE 1234 P. aeruginosa (A) MRSA (C) S.pneumoniae (R) E. faecalis (R) C. jejuni (D) PF-357 S. epidermidis (M)MLTIIIGFIFWTMTLMLGYLIGEREGRK 1235 M. luteus (C) HE MRSA (M) S.pneumoniae (M) PF-360 S. epidermidis (S) MEQKVKVIFVPRSKPDNQLKTFVSAVL1236 E. coli (C) FKA MRSA (H) PF-362 E. coli (C) NIERILKEKVWMIRCVE 1237MRSA (C) PF-363 S. epidermidis (S) SMLSVTVMCLMHASVAANQAMEKKV 1238 E.coli (C) MRSA (H) S. pneumoniae (R) E. faecalis (D) C. jejuni (D) PF-366S. epidermidis (R) ALCSVIKAIELGIINVHLQ 1239 E. coli (C) P. aeruginosa(A) MRSA (D) S. pneumoniae (C) E. faecalis (C) C. jejuni (D) PF-369 S.epidermidis (S) MSEAVNLLRGARYSQRYAKNQVPYEV 1240 E. coli (R) IIEK MRSA(H) E. faecalis (C) PF-370 S. epidermidis (C) VIFLHKESGNLKEIFY 1241 E.coli (R) MRSA (C) PF-373 S. epidermidis (M) HFYLLFER 1242 MRSA (M)PF-374 S. epidermidis (C) HLFFVKGMFILCQKNQINDE 1243 E. coli (C) MRSA (M)E. faecalis (C) PF-375 S. epidermidis (C) MDSAKAQTMRTDWLAVSCLVASAYL 1244E. coli (C) RSMLA MRSA (C) E. faecalis (C) PF-376 S. epidermidis (C)MTVFEALMLAIAFATLIVKISNKNDKK 1245 E. coli (C) MRSA (C) E. faecalis (C)PF-378 S. epidermidis (M) ESAKSNLNFLMQEEWALFLLL 1246 MRSA (M) PF-379 S.epidermidis (C) VFVVLFIIYLASKLLTKLFPIKK 1247 E. coli (C) MRSA (C) E.faecalis (C) PF-380 S. epidermidis (C) KKIIPLITLFVVTLVG 1248 E. coli (C)P. aeruginosa (A) MRSA (D) S. pneumoniae (D) E. faecalis (C) C. jejuni(D) PF-381 S. epidermidis (C) QGANPCQQVGFTVNDPDCRLAKTV 1249 E. coli (R)MRSA (C) E. faecalis (C) PF-382 MRSA (M) KYKCSWCKRVYTLRKDHKTAR 1250PF-383 S. epidermidis (C) WSEIEINTKQSN 1251 E. coli (R) PF-385 E. coli(A) MIKKSILKIKYYVPVLISLTLILSA 1252 PF-386 S. epidermidis (C)FTLTLITTIVAILNYKDKKK 1253 E. coli (C) MRSA (C) E. faecalis (C) PF-387 S.epidermidis (C) GAVGIAFFAGNMKQDKRIADRQNKKS 1254 E. coli (M) EKK MRSA (C)E. faecalis (C) PF-389 S. epidermidis (R) GLQFKEIAEEFHITTTALQQWHKDNGY1255 MRSA (C) PIYNKNNRK S. pneumoniae (D) E. faecalis (R) C. jejuni (R)PF-390 S. epidermidis (D) VVAYVITQVGAIRF 1256 E. coli (C) MRSA (D) S.pneumoniae (D) E. faecalis (D) C. jejuni (D) PF-392 MRSA (S)DPAGCNDIVRKYCK 1257 E. faecalis (A) C. jejuni (A) PF-393 S. epidermidis(R) DLVQSILSEFKKSG 1258 MRSA (C) S. pneumoniae (R) E. faecalis (A) C.jejuni (R) PF-394 MRSA (C) VLKEECYQKN 1259 E. faecalis (A) PF-395 S.epidermidis (C) YCVPLGNMGNMNNKIW 1260 E. coli (R) MRSA (C) PF-396 S.epidermidis (S) LIYTILASLGVLTVLQAILGREPKAVKA 1261 E. coli (C) MRSA (C)E. faecalis (C) PF-397 S. epidermidis (C) VEDLMEDLNA 1262 PF-398 S.epidermidis (C) ILVVLAGILLVVLSYVGISKFKMNC 1263 E. coli (C) MRSA (C) E.faecalis (C) PF-399 S. epidermidis (C) FPIISALLGAIICIAIYSFIVNRKA 1264 E.coli (C) MRSA (C) E. faecalis (C) PF-401 S. epidermidis (C)YWLSRVTTGHSFAFEKPVPLSLTIK 1265 E. coli (R) MRSA (C) E. faecalis (C)PF-403 S. epidermidis (M) LLSTEQLLKYYDGETFDGFQLPSNE 1266 E. coli (R)MRSA (M) PF-404 S. epidermidis (M) VLYFQATVV 1267 MRSA (M) PF-405 MRSA(M) LVRIEVDDLEEWYERNFI 1268 PF-406 S. epidermidis (C)YLEMNADYLSNMDIFDELWEKYLENNK 1269 MRSA (M) PF-407 S. epidermidis (M)KPKNKKEKTVISYEKLLSMY 1270 MRSA (C) S. pneumoniae (R) E. faecalis (R)PF-408 S. epidermidis (M) YCVPLGNMGNMNNKIW 1271 MRSA (M) PF-410 S.epidermidis (C) FALELIALCRNLFIVYFP 1272 E. coli (S) MRSA (M) E. faecalis(C) PF-411 S. epidermidis (C) WVAVAILLNIALQTQLT 1273 E. coli (C) P.aeruginosa (A) MRSA (D) S. pneumoniae (D) E. faecalis (D) C. jejuni (D)PF-413 S. epidermidis (C) TFAGSIKIGVPDLVHVTFNCKR 1274 E. coli (S) MRSA(C) PF-414 S. pneumoniae (H) LLNKKLE 1275 PF-415 S. pneumoniae (D)MIDVTIGQKSKTGAFNASYSICFSGENF 1276 SF PF-416 S. pneumoniae (H)SKAGLYGKIERSDKRE 1277 PF-417 S. epidermidis (M) DSYFRS 1278 MRSA (M) S.pneumoniae (M) PF-418 S. epidermidis (M) FFLVHFYIRKRKGKVSIFLNYF 1279 E.coli (C) MRSA (D) S. pneumoniae (D) E. faecalis (D) C. jejuni (D) PF-419S. pneumoniae (H) VVTGKVGSLPQIK 1280 PF-421 S. pneumoniae (H)KHCFEITDKTDVV 1281 PF-422 S. epidermidis (R) MSRKKYENDEKSQKKLKIGRKSDVFY1282 MRSA (C) GIID S. pneumoniae (C) E. faecalis (R) C. jejuni (R)PF-423 S. pneumoniae (H) AGKKERLLSFREQFLNKNKKK 1283 PF-424 S. pneumoniae(H) IAAFVTSRAFSDTVSPI 1284 PF-425 S. epidermidis (D)MMELVLKTIIGPIVVGVVLRIVDKWLN 1285 E. coli (C) KDK P. aeruginosa (A) C.albicans (A) MRSA (D) S. pneumoniae (D) E. faecalis (D) C. jejuni (D)PF-426 S. epidermidis (D) MLQKYTQMISVTKCIITKNKKTQENVD 1286 E. coli (C)AYN C. albicans (A) MRSA (D) S. pneumoniae (D) E. faecalis (D) C. jejuni(D) PF-427 E. coli (C) YVLEYHGLRATQDVDAFMAL 1287 MRSA (C) S. pneumoniae(R) E. faecalis (C) PF-428 S. pneumoniae (H) ENEESIF 1288 PF-429 S.epidermidis (C) AATLICVGSGIMSSL 1289 MRSA (C) S. pneumoniae (M) E.faecalis (C) PF-430 S. epidermidis (M) AVVCGYLAYTATS 1290 MRSA (M) S.pneumoniae (M) PF-431 S. epidermidis (M) VAYAAICWW 1291 MRSA (C) S.pneumoniae (R) E. faecalis (R) C. jejuni (R) PF-432 S. epidermidis (M)FNGDSEFFLCIAF 1292 E. coli (R) P. aeruginosa (A) MRSA (M) S. pneumoniae(D) E. faecalis (D) C. jejuni (D) PF-433 S. pneumoniae (H)MRKEFHNVLSSGQLLADKRPARDYNRK 1293 PF-434 S. pneumoniae (S)GQLLADKRPARDYNRK 1294 PF-437 S. pneumoniae (I) FQKPFTGEEVEDFQDDDEIPTII1295 PF-439 S. epidermidis (C) RVLVLKKFHGIMDGNRNVAVFFVGQ 1296 E. coli(R) MRSA (M) S. pneumoniae (R) E. faecalis (C) PF-440 S. epidermidis (C)MFIISPDLFNIAVILYILFFIHDILLLILS 1297 E. coli (R) MRSA (C) S. pneumoniae(R) E. faecalis (C) PF-442 MRSA (M) MQIFYIKTKIFLSFFLFLLIFSQCFYKIEE 1298S. pneumoniae (C) PF-443 E. coli (R) KLLYFFNYFENLQQVHLLVQL 1299 MRSA (C)S. pneumoniae (C) PF-444 S. epidermidis (C) MAAKLWEEGKMVYASSASMTKRLKL1300 E. coli (R) AMSKV MRSA (C) S. pneumoniae (R) E. faecalis (C) PF-445S. pneumoniae (M) ASMTKRLKLAMSKV 1301 PF-446 S. pneumoniae (H) SGNEKV1302 PF-447 S. epidermidis (C) IDKSRNKDQFSHIFGLYNICSG 1303 MRSA (C) S.pneumoniae (C) E. faecalis (C) PF-448 S. pneumoniae (I) SLQSQLGPCLHDQRH1304 PF-449 S. pneumoniae (H) MPTTKSKQKGWTNTKKASNTQ 1305 PF-450 MRSA (C)HRNLIILQRTIFI 1306 S. pneumoniae (C) E. faecalis (C) PF-451 S.epidermidis (C) MVNYIIGSYMLYREQNNNEALRKFDIT 1307 E. coli (R) LAM MRSA(C) S. pneumoniae (C) E. faecalis (C) PF-452 S. epidermidis (C)MNNWIKVAQISVTVINEVIDIMKEKQN 1308 E. coli (C) GGK MRSA (C) S. pneumoniae(R) E. faecalis (C) PF-453 S. epidermidis (C) IIQDIAHAFGY 1309 E. coli(C) MRSA (C) S. pneumoniae (C) PF-454 S. epidermidis (C)MSVFVPVTNIFMFIMSPIFNVNLLHFKV 1310 E. coli (R) YI P. aeruginosa (H) MRSA(C) S. pneumoniae (R) E. faecalis (C) PF-455 S. pneumoniae (A)MARNDDDIKKIKGTLGQSPEVYGERK 1311 LPYT PF-456 E. faecalis (A) TCVKPRTIN1312 C. jejuni (A) PF-457 S. pneumoniae (M) INKYHHIA 1313 PF-458 P.aeruginosa (H) ISLIIFIMLFVVALFKCITNYKHQS 1314 MRSA (M) S. pneumoniae (M)PF-459 S. pneumoniae (H) EKRMSFNENQSHRPLL 1315 PF-460 S. epidermidis (C)MEHVLPFQNTPPNIVIIYKDFTHLKSITFS 1316 E. coli (H) MRSA (C) S. pneumoniae(R) E. faecalis (C) PF-461 MRSA (R) MTLAIKNCSVTKCLGFGDFVNDDSDS 1317 S.pneumoniae (R) YFDA E. faecalis (A) PF-462 S. pneumoniae (H) KNKTDTL1318 PF-464 S. pneumoniae (S) VDMVNRFLGN 1319 PF-465 S. pneumoniae (H)KPVGKALEEIADGKIEPVVPKEYLG 1320 PF-466 S. pneumoniae (H) VRKSDQ 1321PF-467 S. pneumoniae (H) YYKDYFKEI 1322 PF-468 S. pneumoniae (H)EDNKDKKDKKDK 1323 PF-469 S. epidermidis (D) YKVNYNNIDNHFNTLRH 1324 E.coli (C) MRSA (D) S. pneumoniae (D) E. faecalis (D) C. jejuni (D) PF-470E. faecalis (A) PYSDSYATRPHWEQHRAR 1325 C. jejuni (A) PF-471 S.epidermidis (C) MVGKIRGVTPRNDLLNANITGQLNLN 1326 E. coli (C) YRLI P.aeruginosa (A) MRSA (D) S. pneumoniae (D) E. faecalis (C) C. jejuni (D)PF-472 MRSA (C) MHISHLLDEVEQTEREKAVNVLENMN 1327 S. pneumoniae (R) GNVIE. faecalis (A) C. jejuni (R) PF-473 S. epidermidis (R)MAADIISTIGDLVKWIIDTVNKFKK 1328 E. coli (C) MRSA (C) S. pneumoniae (H) E.faecalis (R) C. jejuni (R) PF-474 S. epidermidis (C)MHRNLVLVKMEPIPHIMIIANQIGIIIEKA 1329 E. coli (C) P. aeruginosa (A) C.albicans (B) MRSA (D) S. pneumoniae (D) E. faecalis (C) C. jejuni (D)PF-475 S. epidermidis (M) MREKVRFTQAFKLFWTNYFNFKGRSR 1330 C. albicans(B) RSEY MRSA (S) S. pneumoniae (R) E. faecalis (R) C. jejuni (R) PF-476S. pneumoniae (H) WADAQYKLCENCSE 1331 PF-477 S. pneumoniae (H)HKNKLNIPHIKS 1332 PF-478 S. epidermidis (C) HLFILKSHLKPFPPFRYTYD 1333 E.coli (C) MRSA (H) S. pneumoniae (C) PF-479 S. pneumoniae (C)AYILKRREEKNK 1334 PF-480 S. epidermidis (C) MVEILVNTAISVYIVALYTQWLSTRDN1335 E. coli (R) LKA MRSA (C) S. pneumoniae (R) E. faecalis (C) PF-482S. pneumoniae (S) LVGYVRTSGTVRSYKIN 1336 PF-484 E. faecalis (A)HKKDIRKQVFKN 1337 PF-485 S. pneumoniae (A) KNSMSRSIALID 1338 PF-511 S.pneumoniae (H) VMQSLYVKPPLILVTKLAQQN 1339 PF-512 S. pneumoniae (H)SFMPEIQKNTIPTQMK 1340 PF-513 S. pneumoniae (M) SNGVGLGVGIGSGIRF-NH2 1341PF-514 S. epidermidis (C) QRFYKLFYHIDLTNEQALKLFQVK 1342 E. coli (R) S.pneumoniae (M) E. faecalis (C) PF-515 S. pneumoniae (H)DKSTQDKDIKQAKLLAQELGL-NH2 1343 PF-516 S. pneumoniae (H) ASKQASKQASKQASKQ1344 PF-517 S. pneumoniae (M) VKPTMTASLISTVC 1345 PF-518 S. epidermidis(C) SFYSKYSRYIDNLAGAIFLFF 1346 E. coli (R) MRSA (C) S. pneumoniae (M) E.faecalis (C) PF-519 E. coli (R) YLVYSGVLATAAAF-NH2 1347 MRSA (C) S.pneumoniae (S) E. faecalis (C) PF-520 S. pneumoniae (M)LGLTAGVAYAAQPTNQPTNQPTNQPT 1348 NQPTNQPTNQPRW-NH2 PF-521 S. pneumoniae(H) CGKLLEQKNFFLKTR 1349 PF-522 S. pneumoniae (H)FELVDWLETNLGKILKSKSA-NH2 1350 PF-524 E. coli (M)PDAPRTCYHKPILAALSRIVVTDR 1351 MRSA (C) S. pneumoniae (M) E. faecalis (C)PF-525 S. pneumoniae (H) KFSDQIDKGQDALKDKLGDL 1352 PF-526 S. epidermidis(C) VLLLFIFQPFQKQLL-NH2 1353 E. coli (R) C. albicans (C) MRSA (C) S.pneumoniae (R) PF-527 S. epidermidis (M) GSVIKKRRKRMAKKKHRKLLKKTRIQ 1354M. luteus (S) RRRAGK B. subtilis (I) P. aeruginosa (I) C. albicans (B)MRSA (I) S. pneumoniae (H) C. jeikeium (I) C. jejuni (M) PF-528 S.epidermidis (H) LVDVVVLIRRHLPKSCS-NH2 1355 E. coli (H) C. albicans (C)MRSA (H) S. pneumoniae (R) PF-529 S. pneumoniae (H) LSEMERRRLRKRA-NH21356 PF-530 S. epidermidis (H) SKFKVLRKIIIKEYKGELMLSIQKQR 1357 E. coli(R) MRSA (C) S. pneumoniae (R) E. faecalis (C) PF-531 S. epidermidis (I)YIQFHLNQQPRPKVKKIKIFL-NH2 1358 E. coli (M) P. aeruginosa (I) S.pneumoniae (C) PF-532 E. coli (C) KFIYKYKLSFIIYKILIQTLTMELNK 1359 MRSA(C) S. pneumoniae (C) E. faecalis (C) PF-533 S. epidermidis (H)KTPNDKIHKTIIIKHIIL 1360 E. coli (R) MRSA (H) S. pneumoniae (C) E.faecalis (C) PF-534 S. epidermidis (C) KYFHLFYHNIIHYSKQHLSLKVDFKN- 1361E. coli (R) NH2 MRSA (C) S. pneumoniae (R) E. faecalis (C) PF-535 P.aeruginosa (H) NIKTRKRALKIIKQHQRSK 1362 S. pneumoniae (H) PF-536 S.epidermidis (C) MEPIPHIMIIANQIGIIIEKA 1363 E. coli (R) P. aeruginosa (H)MRSA (C) S. pneumoniae (M) E. faecalis (C) PF-537 S. pneumoniae (C)LANDYYKKTKKSW 1364 PF-538 S. pneumoniae (H) KNKKQTDILEKVKEILDKKKKTKSVG1365 QKLY PF-539 MRSA (H) SIILTKKKRRKIPLSIDSQIYKYTFKQ 1366 S. pneumoniae(A) PF-540 S. epidermidis (H) KSILILIKVIFIGQTTIIL 1367 E. coli (R) MRSA(H) S. pneumoniae (R) PF-541 E. coli (H) RRNLNSPNIKTRKRALKIIKQHQRSK 1368S. pneumoniae (H) PF-542 S. pneumoniae (H) KKDNPSLNDQDKNAVLNLLALAK 1369PF-543 S. mutans (S) NILFGIIGFVVAMTAAVIVTAISIAK 1370 S. epidermidis (D)M. luteus (C) E. coli (C) MRSA (D) S. pneumoniae (D) PF-544 S.epidermidis (D) FGEKQMRSWWKVHWFHP 1371 MRSA (D) S. pneumoniae (M) E.faecalis (R) PF-545 B. subtilis (I) RESKLIAMADMIRRRI-NH2 1372 C.albicans (B) E. faecalis (H) C. jeikeium (H) PF-546 S. epidermidis (D)PIIAPTIKTQIQ 1373 E. coli (R) MRSA (D) S. pneumoniae (D) E. faecalis (D)C. jeikeium (D) PF-547 S. epidermidis (R) WSRVPGHSDTGWKVWHRW-NH2 1374 B.subtilis (I) MRSA (M) E. faecalis (R) PF-548 S. epidermidis (M)ARPIADLIHFNSTTVTASGDVYYGPG 1375 M. luteus (A) B. subtilis (C) MRSA (M)S. pneumoniae (D) C. jeikeium (R) C. jejuni (D) PF-549 B. subtilis (D)TGIGPIARPIEHGLDS 1376 MRSA (C) PF-550 B. subtilis (D)STENGWQEFESYADVGVDPRRYVPL 1377 PF-551 MRSA (C)QVKEKRREIELQFRDAEKKLEASVQAE 1378 PF-552 B. subtilis (D)ELDKADAALGPAKNLAPLDVINRS 1379 PF-553 B. subtilis (D)LTIVGNALQQKNQKLLLNQKKITSLG 1380 MRSA (M) S. pneumoniae (R) C. jeikeium(R) PF-554 B. subtilis (D) AKNFLTRTAEEIGEQAVREGNINGP 1381 PF-555 MRSA(M) EAYMRFLDREMEGLTAAYNVKLFTEA 1382 S. pneumoniae (R) IS C. jejuni (R)PF-556 S. epidermidis (A) SLQIRMNTLTAAKASIEAA 1383 M. luteus (A) B.subtilis (C) MRSA (M) S. pneumoniae (D) E. faecalis (A) C. jeikeium (D)C. jejuni (R) PF-557 B. subtilis (D) AANKAREQAAAEAKRKAEEQAR 1384 PF-558S. epidermidis (M) ADAPPPLIVRYS 1385 B. subtilis (D) MRSA (C) S.pneumoniae (R) C. jejuni (H) PF-559 B. subtilis (C)SRPGKPGGVSIDVSRDRQDILSNYP 1386 C. jejuni (A) PF-560 B. subtilis (D)FGNPFRGFTLAMEADFKKRK 1387 MRSA (C) S. pneumoniae (R) C. jejuni (A)PF-561 B. subtilis (D) ESLEADVQAELDTEAAKYPALPASF 1388 MRSA (M) PF-562 S.epidermidis (A) TPEQWLERSTVVVTGLLNRK 1389 M. luteus (R) MRSA (M) S.pneumoniae (D) C. jejuni (R) PF-563 B. subtilis (D)RPELDNELDVVQNSASLDKLQASYN 1390 S. pneumoniae (H) C. jejuni (H) PF-564 B.subtilis (D) TIILNDQINSLQERLNKLNAETDRR 1391 MRSA (C) C. jeikeium (R) C.jejuni (R) PF-565 B. subtilis (D) RAEAEAQRQAEADAKRKAEEAARL 1392 MRSA (C)PF-566 M. luteus (D) EAQQVTQQLGADFNAITTPTATKV 1393 B. subtilis (C) MRSA(M) S. pneumoniae (D) C. jeikeium (C) C. jejuni (D) PF-567 M. luteus (C)QQRVKAVDASLSQVSTQVSGAVASA 1394 MRSA (D) S. pneumoniae (D) C. jeikeium(C) C. jejuni (D) PF-569 B. subtilis (D) KSKISEYTEKEFLEFVEDIYTNNK 1395PF-571 B. subtilis (D) SDLLYYPNENREDSPAGVVKEVKE 1396 PF-572 B. subtilis(D) WRASKGLPGFKAG 1397 S. pneumoniae (R) PF-573 S. pneumoniae (C)EKKLIVKLIDSIGKSHEEIVGAG 1398 PF-574 B. subtilis (D)LVKSGKLESPYEHSEHLTLSQEKGLE 1399 PF-575 P. aeruginosa (A)LNFRAENKILEKIHISLIDTVEGSA 1400 S. pneumoniae (A) C. jeikeium (A) C.jejuni (R) PF-576 S. epidermidis (A) AYSGELPEPLVRKMSKEQVRSVMGK 1401 E.coli (A) MRSA (R) S. pneumoniae (C) C. jejuni (C) PF-577 S. epidermidis(A) PFETRESFRVPVIGILGGWDYFMHP 1402 E. coli (A) P. aeruginosa (A) MRSA(M) S. pneumoniae (R) E. faecalis (A) C. jejuni (R) PF-578 S. mutans (D)QKANLRIGFTYTSDSNVCNLTFALLGSK 1403 S. epidermidis (D) M. luteus (C) P.mirabilis (C) E. coli (C) MRSA (C) S. pneumoniae (D) PF-580 S.epidermidis (M) EILNNNQVIKELTMKYKTQFESNLGG 1404 M. luteus (C) WTARARRMRSA (M) S. pneumoniae (C) PF-581 MRSA (A) WTARARR 1405 S. pneumoniae(A) E. faecalis (A) C. jejuni (A) PF-582 E. faecalis (A)NLKTIEKECPFCNNKMDIKLKD 1406 PF-583 S. mutans (F)KFQGEFTNIGQSYIVSASHMSTSLNTGK 1407 S. epidermidis (I) MRSA (I) S.pneumoniae (D) PF-584 S. epidermidis (C) SYIKNLSNQKFLIAF 1408 E. coli(C) MRSA (D) S. pneumoniae (D) E. faecalis (D) C. jejuni (D) PF-585 S.epidermidis (S) DYNHLLNVVQDWVNTN 1409 MRSA (S) S. pneumoniae (R) E.faecalis (A) C. jejuni (R) PF-586 S. epidermidis (C) FFNQANYFFKEF 1410E. coli (C) MRSA (D) S. pneumoniae (D) E. faecalis (D) C. jejuni (D)PF-587 S. pneumoniae (C) ASGKYQSYLLNVYVDSKKDRLDIFDK 1411 LKAKAKFVLPF-588 E. faecalis (A) ESVEAIKAKAIK 1412 PF-589 MRSA (M)APLRIDEIRNSNVIDEVLDCAPKKQEHF 1413 S. pneumoniae (C) FVVPKIIE PF-590 C.jejuni (R) YYQAKLFPLL 1414 PF-591 S. pneumoniae (R)DLLKSLLGQDGAKNDEIIEFIKIIMEK 1415 E. faecalis (A) C. jejuni (C) PF-592 S.epidermidis (M) IMKNYKYFKLFIVKYALF 1416 E. coli (C) MRSA (D) S.pneumoniae (D) E. faecalis (D) C. jejuni (S) PF-593 E. faecalis (A)MEISTLKKEKLHVKDELSQYLANYKK 1417 PF-594 E. faecalis (C) IVSAIV 1418PF-595 S. epidermidis (C) LQNKIYELLYIKERSKLCS 1419 E. coli (C) MRSA (D)S. pneumoniae (R) E. faecalis (D) C. jejuni (D) PF-596 S. epidermidis(D) SKMWDKILTILILILELIRELIKL 1420 E. coli (C) MRSA (D) S. pneumoniae (D)E. faecalis (D) C. jejuni (D) PF-597 E. faecalis (A) DEIKVSDEEIEKFIKENNL1421 PF-598 S. epidermidis (R) MKFMLEVRNKAISAYKEITRTQI 1422 E. coli (C)MRSA (D) S. pneumoniae (R) E. faecalis (R) C. jejuni (R) PF-599 S.epidermidis (M) LFEIFKPKH 1423 MRSA (C) S. pneumoniae (R) E. faecalis(A) C. jejuni (R) PF-600 S. mutans (S) TKKIELKRFVDAFVKKSYENYILEREL 1424S. epidermidis (C) KKLIKAINEELPTK M. luteus (C) E. coli (H) MRSA (M) S.pneumoniae (R) PF-601 E. faecalis (A) YRVTVKALE 1425 C. jejuni (A)PF-602 E. faecalis (A) LEKEKKEYIEKLFKTK 1426 PF-603 S. epidermidis (D)IDKLKKMNLQKLSYEVRISQDGKSIYA 1427 M. luteus (A) RIK E. coli (M) MRSA (M)S. pneumoniae (C) PF-604 E. faecalis (A) LMEQVEV 1428 PF-605 S.epidermidis (R) HYRWNTQWWKY 1429 E. coli (C) P. aeruginosa (A) C.albicans (B) MRSA (C) S. pneumoniae (D) E. faecalis (R) C. jejuni (R)PF-606 S. mutans (I) FESKILNASKELDKEKKVNTALSFNSH 1430 S. epidermidis (I)QDFAKAYQNGKI C. albicans (B) MRSA (I) S. pneumoniae (H) PF-607 S.epidermidis (M) YIESDPRKFDYIFGAIRDH 1431 MRSA (S) S. pneumoniae (R) E.faecalis (A) C. jejuni (R) PF-609 MRSA (C) TEIKLDNNEYLVLNLDDILGILK 1432S. pneumoniae (R) E. faecalis (A) C. jejuni (R) PF-610 S. epidermidis(C) VFLKLKTSKIDLASIIFYP 1433 E. coli (C) MRSA (D) S. pneumoniae (D) E.faecalis (D) C. jejuni (D) PF-612 S. mutans (F)GTTLKYGLERQLKIDIHPEITIINLNGGA 1434 S. epidermidis (C) DEFAKL M. luteus(A) P. mirabilis (C) E. coli (C) MRSA (C) S. pneumoniae (C) PF-613 S.epidermidis (R) ADEFAKL 1435 MRSA (C) E. faecalis (A) PF-614 S.epidermidis (M) GLDIYA 1436 S. pneumoniae (R) E. faecalis (A) C. jejuni(R) PF-615 S. epidermidis (D) FLNRFIFYIFTVKTKSALIKNLFLD 1437 E. coli (C)MRSA (D) S. pneumoniae (D) E. faecalis (D) C. jejuni (D) PF-616 S.epidermidis (R) IVFVVTKEKK 1438 E. faecalis (A) PF-617 C. albicans (H)PMNAAEPE 1439 S. pneumoniae (I) E. faecalis (H) PF-618 S. pneumoniae (I)KLNTLNKKDNPSLNDQDKNAVLNLLA 1440 E. faecalis (H) LAK PF-619 S.epidermidis (M) WSRVPGHSDTGWKVWHRW 1441 E. coli (C) MRSA (M) S.pneumoniae (C) PF-621 S. pneumoniae (I) PPSSFLV 1442 E. faecalis (H)PF-622 S. epidermidis (D) TREDVFSVRLINNIVNKQA 1443 MRSA (D) S.pneumoniae (M) E. faecalis (D) C. jeikeium (D) PF-623 S. epidermidis (M)VLFAVYLGALDWLFSWLTQKM 1444 MRSA (D) S. pneumoniae (D) E. faecalis (D) C.jeikeium (R) PF-624 S. mutans (D) VFLLDSYCFVKINL 1445 S. epidermidis (D)M. luteus (C) P. mirabilis (C) E. coli (C) MRSA (C) S. pneumoniae (D)PF-625 S. pneumoniae (H) SDSTNNARTRKKARDVTTKDIDK 1446 PF-626 S.pneumoniae (H) KYDFDDFEPEEA 1447 PF-627 S. epidermidis (H) INDLLSYFTLHEK1448 C. albicans (B) MRSA (R) S. pneumoniae (I) E. faecalis (H) PF-629S. epidermidis (C) GLAAIATVFALY 1449 MRSA (D) S. pneumoniae (M) E.faecalis (R) C. jeikeium (R) PF-630 MRSA (M) IPATPIIHS 1450 PF-631 S.pneumoniae (I) LIIYFSKTGNTARATRQI 1451 E. faecalis (H) PF-632 S.epidermidis (D) TTIQGVASLEKHGFRYTIIYPTRI 1452 B. subtilis (H) C.albicans (B) MRSA (D) S. pneumoniae (M) E. faecalis (D) C. jeikeium (D)PF-634 S. mutans (D) MPKARPVNHNKKKSKITIKSNFTLFYM 1453 S. epidermidis (D)FNP M. luteus (C) P. mirabilis (C) E. coli (C) MRSA (D) S. pneumoniae(D) PF-635 S. epidermidis (M) MNAHGHSLIFQKMIVHAFAFFSKQKN 1454 C.albicans (B) YLYF MRSA (D) S. pneumoniae (D) E. faecalis (D) C. jeikeium(D) PF-636 B. subtilis (H) LVRLA 1455 C. albicans (B) S. pneumoniae (H)E. faecalis (H) PF-637 S. epidermidis (M) SRIKQDARSVRKYDRIGIFFYSFKSA1456 MRSA (M) S. pneumoniae (M) E. faecalis (D) C. jeikeium (D) PF-638S. epidermidis (R) TFILPK 1457 MRSA (M) S. pneumoniae (I) E. faecalis(H) PF-639 C. albicans (B) QATQIKSWIDRLLVSED 1458 MRSA (R) S. pneumoniae(I) E. faecalis (H) PF-640 C. albicans (B) MGDINRNF 1459 S. pneumoniae(I) E. faecalis (H) PF-642 MRSA (M) FTTPMIGIPAGLLGGSYYLKRREEKGK 1460PF-643 MRSA (C) VRCRL 1461 S. pneumoniae (R) E. faecalis (R) PF-644 S.pneumoniae (H) TSGLIIGENGLNGL 1462 PF-645 C. albicans (B) SNSVQQG 1463S. pneumoniae (I) PF-646 C. albicans (B) APASPGRRPG 1464 S. pneumoniae(H) PF-647 C. albicans (B) GTFLGQKCAAATAS 1465 S. pneumoniae (R) PF-649E. faecalis (R) CPRYPFVDVGPAGPWRARWRVGS 1466 PF-651 S. pneumoniae (H)PRWPTGAGRHR 1467 PF-652 S. pneumoniae (A) FLAPARPDLQAQRQALAQ 1468 PF-653S. pneumoniae (H) QSVHPLPAETPVADVI 1469 PF-654 C. albicans (B) LSGRLAGRR1470 MRSA (R) S. pneumoniae (A) PF-655 S. epidermidis (R)DAPCFDDQFGDLKCQMC 1471 B. subtilis (H) MRSA (M) S. pneumoniae (H) PF-656MRSA (R) RGMFVPFHDVDCVQ 1472 PF-657 S. epidermidis (C)YVANYTITQFGRDFDDRLAVAIHFA 1473 MRSA (D) S. pneumoniae (H) E. faecalis(D) C. jeikeium (D) PF-658 MRSA (R) PTTPPPTTPPEIPTGGTVIST 1474 S.pneumoniae (H) PF-659 S. epidermidis (M) TVIST 1475 B. subtilis (H) MRSA(R) S. pneumoniae (C) PF-660 S. pneumoniae (H) TDPQATAAPRRRTSPR 1476PF-661 MRSA (R) PDEDIRRRAILPPAGPCRPMSPE 1477 PF-662 S. pneumoniae (A)GKQSRAHGPVASRREFRRKSG 1478 PF-663 S. pneumoniae (A) ATLIPRKA 1479 PF-664S. epidermidis (M) DQLCVEYPARVSTG 1480 MRSA (R) S. pneumoniae (M) E.faecalis (R) PF-665 S. pneumoniae (H) VLRVATAVGEVPTGL 1481 PF-666 S.pneumoniae (A) PNRRSRPR 1482 PF-667 S. epidermidis (R)PAHQRLRIDQRLVADRDMVQDYES 1483 MRSA (R) S. pneumoniae (R) E. faecalis (R)PF-668 S. epidermidis (M) TNAESMALAFRGRVHMSVNIAGLT 1484 B. subtilis (A)C. albicans (A) MRSA (R) S. pneumoniae (M) E. faecalis (D) C. jeikeium(D) PF-670 B. subtilis (H) TVIVAPMHSGV 1485 S. pneumoniae (H) PF-672 S.epidermidis (I) MRFGSLALVAYDSAIKHSWPRPSSVRR 1486 B. subtilis (I) LRM C.albicans (I) MRSA (I) S. pneumoniae (I) E. faecalis (I) C. jeikeium (R)PF-675 S. pneumoniae (C) EIIPISPTRRCEMHTMSSAEYRGL 1487 E. faecalis (R)PF-677 S. epidermidis (R) TCRGAGMH 1488 MRSA (D) S. pneumoniae (D) E.faecalis (R) PF-680 MRSA (R) ADPHPTTGI 1489 PF-681 S. epidermidis (M)TALTTVGVSGARLITYCVGVEDI 1490 MRSA (M) S. pneumoniae (M) E. faecalis (R)C. jeikeium (R) PF-682 S. pneumoniae (A) RRGKSEQGLSRR 1491 PF-683 S.epidermidis (R) LWPVA 1492 MRSA (R) S. pneumoniae (H) PF-684 C. albicans(B) RKLSLASGFALWRRSLV 1493 S. pneumoniae (C) E. faecalis (A) PF-685 S.epidermidis (M) PTLWLACL 1494 MRSA (M) S. pneumoniae (M) E. faecalis (R)C. jeikeium (R) PF-686 S. epidermidis (H) LAVLMGYIGYRGWSGKRHINRQ 1495 B.subtilis (I) C. albicans (B) MRSA (M) S. pneumoniae (A) E. faecalis (R)PF-687 S. pneumoniae (A) AKRVLSLAVAPHRRQPVQGT 1496 PF-688 S. pneumoniae(A) ARNHAVIPAG 1497 PF-690 S. epidermidis (R)MIPLAGDPVSSHRTVEFGVLGTYLVSG 1498 MRSA (R) GSL S. pneumoniae (M) E.faecalis (R) PF-691 S. pneumoniae (R) HRTVEFGVLGTYLVSGGSL 1499 PF-692MRSA (R) GVAREDPLEPDPLAPIIDDSR 1500 PF-693 S. pneumoniae (A) PDPAR 1501PF-694 MRSA (R) DLIRPLYSMSAPSVA 1502 S. pneumoniae (A) PF-695 MRSA (R)ALSVMLGNIPLVVPNANQL 1503 S. pneumoniae (C) E. faecalis (R) PF-696 S.pneumoniae (H) IRSGISAAYARPLR 1504 PF-697 C. albicans (H) RADARAK 1505S. pneumoniae (H) PF-698 C. albicans (H) SSGRAGVKCRRPTGR 1506 S.pneumoniae (A) E. faecalis (A) PF-699 S. pneumoniae (A) GRAGVKCRRPTGR1507 PF-700 S. pneumoniae (C) LNWPFTGR 1508 PF-702 S. pneumoniae (H)LSGRLAGRR 1509 PF-704 S. pneumoniae (C) APAARAAL 1510 PF-737 S.pneumoniae (D) KSSGSSASASSTAGGSSSK 1511 PF-738 MRSA (M)KSGATSAASGAKSGASS 1512 PF-741 S. mutans (D) AKREDTVAAQIGANILNLIQ 1513 S.epidermidis (C) M. luteus (C) P. mirabilis (C) E. coli (C) MRSA (C) S.pneumoniae (D) PF-744 S. pneumoniae (H) LGVGTFVGKVLIKNQQKQKSKKKAQ 1514PF-745 S. mutans (D) ANSQNSLFSNRSSFKSIFDKKSNITTNA 1515 M. luteus (C)TTPNSNIIIN MRSA (C) S. pneumoniae (C) PF-746 S. mutans (D) FLGNSQYFTRK1516 S. epidermidis (C) M. luteus (C) E. coli (C) P. aeruginosa (A) MRSA(C) S. pneumoniae (C) PF-748 S. pneumoniae (H) FQGFFDVAVNKWWEEHNKAKLWKN1517 VKGKFLEGEGEEEDDE PF-749 S. pneumoniae (H) GVNKWWEEHNKAKLWKNVKGKFLE1518 GEGEEEDDE PF-752 S. pneumoniae (C) LHVIRPRPELSELKFPITKILKVNKQGL1519 KK PF-756 S. pneumoniae (A) DALLRLA 1520 PF-757 S. pneumoniae (H)PQAISSVQQNA 1521 PF-760 S. epidermidis (M) DHITLDDYEIHDGFNFELYYG 1522MRSA (M) S. pneumoniae (C) PF-761 S. mutans (D)SKFELVNYASGCSCGADCKCASETECK 1523 S. epidermidis (C) CASKK M. luteus (C)E. coli (C) P. aeruginosa (C) MRSA (D) S. pneumoniae (C) PF-762 S.pneumoniae (H) PAPAPSAPAPAPEQPEQPA 1524 PF-763 S. epidermidis (M)GIWMARNYFHRSSIRKVYVESDKEYE 1525 M. luteus (C) RVHPMQKIQYEGNYKSQ MRSA (D)S. pneumoniae (C) PF-764 MRSA (D) GYFEPGKRD 1526 S. pneumoniae (H)PF-770 S. mutans (D) GVGIGFIMMGVVGYAVKLVHIPIRYLIV 1527 S. epidermidis(D) M. luteus (C) P. mirabilis (C) E. coli (C) MRSA (D) S. pneumoniae(C) PF-776 S. mutans (D) VSILLYLSATIILPNVLRLLVARAIIVRV 1528 S.epidermidis (D) M. luteus (C) E. coli (C) MRSA (D) S. pneumoniae (C)PF-C052 P. gingivalis (H) SRFRNGV 1529 PF-C055 F. nucleatum (T)YNLSIYIYFLHTITIAGLITLPFII 1530 S. mutans (I) PF-C057 S. mutans (I)YFWWYWVQDCIPYKNNEVWLELSNN 1531 MK PF-C058 S. mutans (F)FETGFGDGYYMSLWGLNEKDEVCKV 1532 VIPFINPELID PF-C061 F. nucleatum (T)TLNYKKMFFSVIFLLGLNYLICNSPLFF 1533 S. mutans (F) KQIEF PF-C062 F.nucleatum (T) PLARATEVVATLFIICSLLLYLTR 1534 S. mutans (I) PF-C064 F.nucleatum (T) DEEALEMGANLYAQFAIDFLNSKK 1535 PF-C065 F. nucleatum (T)DEERYSDSYFLKEKVFYLILALFLILFH 1536 QKYLYFLEIITI PF-C069 F. nucleatum (T)NALMLREMQLAKNIKVEVTDVLSNKK 1537 YC PF-C071 F. nucleatum (T) QVIVKIL 1538PF-C072 F. nucleatum (T) KKMFSLIRKVNWIFFILFIVLDLTNVFP 1539 P. gingivalis(T) LIRTILFAILSRQ S. mutans (F) PF-C075 F. nucleatum (T)KALVISVFAIVFSIIFVKFFYWRDKK 1540 P. gingivalis (R) S. mutans (F) PF-C084F. nucleatum (T) FFSVIFLFGLNYLICNSPLFNILR 1541 P. gingivalis (R) S.mutans (F) PF-C085 S. mutans (F) KKFKIFVIINWFYHKYIILNFEENF 1542 PF-C086F. nucleatum (T) ELFFTILSDCNELFLLHLLQQPLFYIKK 1543 GK PF-C088 F.nucleatum (H) DIANNILNSVSERLIIA 1544 P. gingivalis (R) S. mutans (I)PF-C089 P. gingivalis (R) MPKRHYYKLEAKALQFGLPFAYSPIQL 1545 LK PF-C091 F.nucleatum (T) ASNTPRFVRLTLFNFYSKIWNVTHLFLF 1546 NNL PF-C095 F. nucleatum(T) LLALNMNEDTYYFELFFIFDNQNKKW 1547 LIFDLKERG PF-C098 F. nucleatum (T)PETKGKVSAFVFGIVVANVIAVVYILY 1548 S. mutans (F) MLREIGIIQ PF-C120 F.nucleatum (T) ASLSTMTFKVMELKELIILLCGLTMLMI 1549 QTEFV PF-C131 F.nucleatum (T) QWIVAKREIRMHIYCHISVIHVIIFFG 1550 S. mutans (F) PF-C135 F.nucleatum (C) KNTHAYLRVLRLSSLILSYQASVYPLF 1551 S. mutans (F) AYLCQQKDYPF-C136 F. nucleatum (C) LILSYQASVYPLFAYLCQQKDY 1552 P. gingivalis (R)PF-C137 F. nucleatum (T) QRMYWFKRGFETGDFSAGDTFAELK 1553 PF-C139 S.mutans (F) LLASHPERLSLGVFFVYRVLHLLLENT 1554 PF-C142 S. mutans (I)DFPPLSFFRRRFHAYTAPIDNFFGANPF 1555 PF-C143 F. nucleatum (C) VVFGGGDRLV1556 PF-C145 F. nucleatum (C) YGKESDP 1557 S. mutans (I) PF-C180 P.gingivalis (R) TVEELDKAFTWGAAAALAIGVIAINVG 1558 S. mutans (S)LAAGYCYNNNDVF PF-C181 F. nucleatum (T) KMRAGQVVFIYKLILVLLFYVLQKLFD 1559LKKGCF PF-C194 F. nucleatum (T) NTNDLLQAFELMGLGMAGVFIVLGILY 1560 P.gingivalis (T) IVAELLIKIFPVNN S. mutans (F) PF-C214 F. nucleatum (T)GGHKQLVIEPLVSQ 1561 PF-C281 S. mutans (F) KKEKLLTAIRLQHRAEIRGYFTIFFLFFRI1562 PF-C290 S. mutans (F) GNVHPESDFHNLIQFIKTFLYFTIFFKYFL 1563 PF-C291F. nucleatum (T) HPFLTGTGCPLFLIFRLFFVKAYFSFTVF 1564 S. mutans (F)PF-C293 F. nucleatum (T) IIIILPKIYLVCKTV 1565 P. gingivalis (R) S.mutans (F) PF-S003 S. epidermidis (R) ALALLKQDLLNFEGRGRIITSTYLQFNE 1566M. luteus (R) GCVP B. subtilis (A) P. aeruginosa (A) C. albicans (A)MRSA (M) S. pneumoniae (D) C. jeikeium (D) C. jejuni (D) Key toAbbreviations: (A) Peptide aggregates; (B) Less hyphal formation; (C)Clumps; (D) Diffuse clumps and small polyps; (F) Diffuse growth; (H)Thin; (I) Growth inhibition; (M) Microcolony formation; (R) Rippled; (S)Small polyps; (T) Thick; (W) Halo formation on top, microlonies onbottom. These data thus indicate peptide-mediated interruption ofbacterial biofilm formation processes, cellular metabolism, cellularimport/export, nutrient acquisition, quorum sensing and communication,motility, chemotaxis, replication, translation, and/or transcription.Accordingly, without being bound to a particular theory, it is believedthat the alteration of one or more of these basic pathways is importantto pathogenesis, or the stopping thereof.

In certain embodiments, the amino acid sequence of the antimicrobialpeptides comprises or consists of a single amino acid sequence, e.g., aslisted above in Tables 4 and/or 5, and/or Table 15, and/or below inTable 14. In certain embodiments the amino acid sequence of theantimicrobial peptides comprises two copies, three copies, four copies,five copies six copies or more of one or more of the amino acidsequences listed in Tables 4, and/or 5, and/or Table 15, and/or Table14. Thus, compound antimicrobial constructs are contemplated where theconstruct comprises multiple domains each having antimicrobial activity.The AMP domains comprising such a construct can be the same ordifferent. In certain embodiments the construct comprises at least 2, atleast 3, at least 4, at least 5, at least 6, at least 7, or at least 8different AMP domains each domain comprising a different AMP sequence.

Various AMP domains comprising such a construct can be joined directlyto each other or two or more of such domains can be attached to eachother via a linker. An illustrative, but non-limiting, list of suitablelinkers is provided in Table 16. Thus, in certain embodiments, two ormore AMP domains comprising a compound AMP construct are chemicallyconjugated together.

In certain embodiments the two or more AMP domains comprising the AMPconstruct are joined by a peptide linker. Where all the AMP domains areattached directly to each other or are joined by peptide linkers, theentire construct can be provided as a single-chain peptide (fusionprotein).

In various embodiments, the antimicrobial peptides described hereincomprise one or more of the amino acid sequences shown in Tables 4,and/or 5, and/or 15 and/or 14 (and/or the retro, inverso, retroinverso,etc. forms of such sequences). In certain embodiments the peptides rangein length up to about 100 amino acids in length, preferably up to about80, about 70, about 60, or about 51 amino acids in length. In certainembodiments the peptides range in length from about 8 amino acids up toabout 100 amino acids 80 amino acids, 60 amino acids or about 51 aminoacids in length. In certain embodiments the peptides range in lengthfrom about 8 up to about 50, 40, 30, 20, 15, 15, 13, or 12 amino acidsin length.

As shown in Tables 4, and/or 5, and/or 15 and/or 14, the various aminoacid sequences described herein are effective against particularmicroorganisms. The range of activity of the peptides or compositionscomprising such peptides can be increased by including amino acidsequences effective against different microorganisms either as separatecomponents and/or as multiple domains within a single construct.

TABLE 6 Illustrative target microorganisms and peptides effectiveagainst that target. Gram Positive Bacteria: A. naeslundii PF-531,PF-527, PF-672, PF-545, PF-168, PF-448, PF-525, PF-529, PF- 148 B.subtilis PF-002, PF-005, PF-006, PF-040, PF-053, PF-056, PF-061, PF-063,PF- 067, PF-068, PF-069, PF-070, PF-071, PF-145, PF-148, PF-171, PF-175,PF-283, PF-289, PF-292, PF-296, PF-297, PF-301, PF-303, PF-305, PF- 306,PF-307, PF-318, PF-319, PF-322, PF-335, PF-339, PF-342, PF-497, PF-499,PF-527, PF-531, PF-545, PF-547, PF-548, PF-549, PF-550, PF- 552, PF-553,PF-554, PF-556, PF-557, PF-558, PF-559, PF-560, PF-561, PF-563, PF-564,PF-565, PF-566, PF-569, PF-571, PF-572, PF-574, PF- 632, PF-636, PF-655,PF-659, PF-668, PF-670, PF-672, PF-686, PF-998, PF-2003 C. difficilePF-522, PF-531, PF-538 C. jeikeium PF-001, PF-003, PF-004, PF-101,PF-011, PF-012, PF-013, PF-021, PF- 022, PF-025, PF-028, PF-030, PF-032,PF-033, PF-036, PF-037, PF-040, PF-042, PF-043, PF-046, PF-048, PF-052,PF-053, PF-056, PF-057, PF- 063, PF-065, PF-067, PF-068, PF-073, PF-075,PF-076, PF-099, PF-124, PF-127, PF-129, PF-133, PF-135, PF-137, PF-139,PF-140, PF-145, PF- 148, PF-164, PF-173, PF-176, PF-186, PF-188, PF-190,PF-191, PF-196, PF-199, PF-203, PF-204, PF-208, PF-527, PF-531, PF-545,PF-546, PF- 548, PF-553, PF-556, PF-564, PF-566, PF-567, PF-575, PF-622,PF-523, PF-629, PF-632, PF-635, PF-637, PF-657, PF-668, PF-672, PF-681,PF- 685, PF-S003 E. faecalis PF-007, PF-053, PF-057, PF-068, PF-347,PF-349, PF-355, PF-356, PF- 363, PF-366, PF-369, PF-374, PF-375, PF-376,PF-379, PF-380, PF-381, PF-386, PF-387, PF-389, PF-390, PF-392, PF-393,PF-394, PF-396, PF- 398, PF-399, PF-401, PF-407, PF-410, PF-411, PF-418,PF-422, PF-425, PF-426, PF-427, PF-429, PF-431, PF-432, PF-439, PF-440,PF-444, PF- 447, PF-450, PF-451, PF-452, PF-454, PF-456, PF-460, PF-461,PF-469, PF-470, PF-471, PF-472, PF-473, PF-474, PF-475, PF-480, PF-484,PF- 514, PF-518, PF-519, PF-524, PF-530, PF-532, PF-533, PF-534, PF-536,PF-544, PF-545, PF-546, PF-547, PF-556, PF-577, PF-581, PF-582, PF- 584,PF-585, PF-586, PF-588, PF-591, PF-592, PF-593, PF-594, PF-595, PF-596,PF-597, PF-598, PF-599, PF-601, PF-602, PF-604, PF-605, PF- 607, PF-609,PF-610, PF-613, PF-614, PF-615, PF-616, PF-617, PF-618, PF-621, PF-622,PF-623, PF-627, PF-629, PF-631, PF-632, PF-635, PF- 636, PF-637, PF-638,PF-639, PF-640, PF-643, PF-649, PF-657, PF-664, PF-667, PF-668, PF-672,PF-675, PF-677, PF-681, PF-684, PF-685, PF- 686, PF-690, PF-695, PF-698M. luteus PF-001, PF-003, PF-004, PF-006, PF-007, PF-010, PF-012,PF-013, PF- 020, PF-021, PF-022, PF-025, PF-030, PF-036, PF-037, PF-040,PF-042, PF-043, PF-051, PF-052, PF-053, PF-056, PF-057, PF-063, PF-067,PF- 068, PF-071, PF-073, PF-075, PF-076, PF-125, PF-127, PF-137, PF-139,PF-140, PF-145, PF-148, PF-171, PF-175, PF-176, PF-199, PF-204, PF- 212,PF-215, PF-224, PF-226, PF-234, PF-235, PF-249, PF-250, PF-255, PF-257,PF-264, PF-270, PF-271, PF-274, PF-276, PF-278, PF-357, PF- 527, PF-543,PF-548, PF-556, PF-562, PF-566, PF-567, PF-578, PF-580, PF-600, PF-603,PF-612, PF-624, PF-634, PF-741, PF-745, PF-746, PF- 761, PF-763, PF-770,PF-776, PF-S003 MRSA PF-001, PF-003, PF-004, PF-006, PF-007, PF-010,PF-011, PF-012, PF- 013, PF-015, PF-017, PF-019, PF-020, PF-021, PF-022,PF-023, PF-024, PF-025, PF-026, PF-027, PF-028, PF-029, PF-030, PF-031,PF-033, PF- 035, PF-036, PF-037, PF-040, PF-041, PF-042, PF-043, PF-045,PF-046, PF-048, PF-049, PF-051, PF-052, PF-053, PF-056, PF-057, PF-058,PF- 063, PF-064, PF-065, PF-066, PF-067, PF-068, PF-071, PF-073, PF-074,PF-075, PF-076, PF-140, PF-145, PF-148, PF-149, PF-156, PF-168, PF- 171,PF-178, PF-191, PF-209, PF-347, PF-349, PF-350, PF-354, PF-355, PF-356,PF-357, PF-360, PF-362, PF-366, PF-369, PF-370, PF-373, PF- 374, PF-375,PF-376, PF-378, PF-379, PF-380, PF-381, PF-382, PF-386, PF-387, PF-389,PF-390, PF-392, PF-393, PF-394, PF-395, PF-396, PF- 398, PF-399, PF-401,PF-403, PF-404, PF-405, PF-406, PF-407, PF-408, PF-410, PF-411, PF-413,PF-417, PF-418, PF-422, PF-425, PF-426, PF- 427, PF-429, PF-430, PF-431,PF-432, PF-439, PF-440, PF-442, PF-443, PF-444, PF-447, PF-450, PF-451,PF-452, PF-453, PF-454, PF-458, PF- 460, PF-461, PF-469, PF-471, PF-472,PF-473, PF-474, PF-475, PF-478, PF-480, PF-518, PF-519, PF-524, PF-526,PF-527, PF-528, PF-530, PF- 532, PF-533, PF-534, PF-536, PF-539, PF-540,PF-543, PF-544, PF-545, PF-546, PF-547, PF-548, PF-549, PF-551, PF-553,PF-555, PF-556, PF- 558, PF-560, PF-561, PF-562, PF-564, PF-565, PF-566,PF-567, PF-576, PF-577, PF-578, PF-580, PF-581, PF-583, PF-584, PF-585,PF-586, PF- 589, PF-592, PF-595, PF-596, PF-598, PF-599, PF-600, PF-603,PF-605, PF-606, PF-607, PF-609, PF-610, PF-612, PF-613, PF-615, PF-619,PF- 622, PF-623, PF-624, PF-627, PF-629, PF-630, PF-632, PF-634, PF-635,PF-637, PF-638, PF-639, PF-652, PF-643, PF-654, PF-655, PF-656, PF- 657,PF-658, PF-659, PF-661, PF-664, PF-667, PF-778, PF-672, PF-677, PF-680,PF-683, PF-685, PF-686, PF-690, PF-692, PF-694, PF-695, PF- 738, PF-741,PF-745, PF-746, PF-760, PF-761, PF-763, PF-764, PF-770, PF-776, PF-S003S. epidermidis PF-001, PF-003, PF-004, PF-006, PF-007, PF-009, PF-010,PF-012, PF- 013, PF-020, PF-021, PF-022, PF-024, PF-025, PF-027, PF-028,PF-030, PF-032, PF-033, PF-034, PF-036, PF-037, PF-040, PF-041, PF-042,PF- 043, PF-046, PF-048, PF-051, PF-052, PF-953, PF-956, PF-957, PF-961,PF-963, PF-964, PF-965, PF-967, PF-968, PF-971, PF-073, PF-074, PF- 075,PF-076, PF-099, PF-123, PF-124, PF-125, PF-127, PF-128, PF-129, PF-137,PF-139, PF-140, PF-145, PF-148, PF-153, PF-157, PF-171, PF- 173, PF-176,PF-178, PF-180, PF-186, PF-190, PF-191, PF-192, PF-196, PF-199, PF-203,PF-204, PF-208, PF-209, PF-226, PF-233, PF-273, PF- 278, PF-283, PF-290,PF-292, PF-293, PF-294, PF-296, PF-297, PF-301, PF-307, PF-310, PF-313,PF-318, PF-319, PF-322, PF-335, PF-339, PF- 342, PF-347, PF-349, PF-350,PF-355, PF-356, PF-357, PF-360, PF-363, PF-366, PF-369, PF-370, PF-373,PF-374, PF-375, PF-376, PF-378, PF- 379, PF-380, PF-381, PF-383, PF-386,PF-387, PF-389, PF-390, PF-393, PF-395, PF-396, PF-397, PF-398, PF-399,PF-401, PF-403, PF-404, PF- 406, PF-407, PF-408, PF-410, PF-411, PF-413,PF-417, PF-418, PF-422, PF-425, PF-246, PF-249, PF-430, PF-431, PF-432,PF-439, PF-440, PF- 444, PF-447, PF-451, PF-452, PF-453, PF-454, PF-460,PF-469, PF-471, PF-473, PF-474, PF-475, PF-478, PF-480, PF-514, PF-518,PF-526, PF- 527, PF-528, PF-530, PF-531, PF-533, PF-534, PF-536, PF-540,PF-543, PF-544, PF-546, PF-547, PF-548, PF-556, PF-558, PF-562, PF-576,PF- 577, PF-578, PF-580, PF-583, PF-584, PF-585, PF-586, PF-592, PF-595,PF-596, PF-598, PF-599, PF-600, PF-603, PF-605, PF-606, PF-607, PF- 610,PF-612, PF-613, PF-614, PF-615, PF-616, PF-619, PF-622, PF-623, PF-624,PF-627, PF-632, PF-634, PF-635, PF-637, PF-638, PF-655, PF- 657, PF-659,PF-664, PF-667, PF-778, PF-672, PF-677, PF-681, PF-683, PF-685, PF-686,PF-690, PF-741, PF-746, PF-760, PF-761, PF-763, PF- 770, PF-776, PF-S003S. mutans G-1, G-2, G-4, G-8, PF-020, PF-040, PF-051, PF-531, PF-543,PF-547, PF-578, PF-583, PF-600, PF-606, PF-612, PF-624, PF-634, PF-741,PF- 745, PF-746, PF-761, PF-770, PF-776, PF-C055, PF-C057, PF-C058, PF-C061, PF-C062, PF-C072, PF-C075, PF-C084, PF-C085, PF-C088, PF- C098,PF-C131, PF-C135, PF-C139, PF-C142, PF-C146, PF-C180, PF- C194, PF-C281,PF-C290, PF-C291, PF-C293 S. pneumoniae PF-002, PF-005, PF-006, PF-020,PF-033, PF-040, PF-051, PF-053, PF- 056, PF-057, PF-061, PF-063, PF-068,PF-071, PF-073, PF-140, PF-144, PF-145, PF-148, PF-171, PF-175, PF-178,PF-220, PF-355, PF-356, PF- 357, PF-363, PF-366, PF-380, PF-389, PF-390,PF-393, PF-407, PF-411, PF-414, PF-415, PF-416, PF-417, PF-418, PF-419,PF-421, PF-422, PF- 423, PF-424, PF-425, PF-426, PF-427, PF-428, PF-429,PF-430, PF-431, PF-432, PF-433, PF-434, PF-437, PF-439, PF-440, PF-442,PF-443, PF- 444, PF-445, PF-446, PF-447, PF-448, PF-449, PF-450, PF-451,PF-452, PF-453, PF-454, PF-455, PF-457, PF-458, PF-469, PF-460, PF-461,PF- 462, PF-464, PF-465, PF-466, PF-467, PF-468, PF-469, PF-471, PF-472,PF-473, PF-474, PF-475, PF-476, PF-477, PF-478, PF-479, PF-480, PF- 482,PF-485, PF-511, PF-512, PF-513, PF-514, PF-515, PF-516, PF-517, PF-518,PF-519, PF-520, PF-521, PF-522, PF-523, PF-524, PF-525, PF- 526, PF-527,PF-528, PF-529, PF-530, PF-531, PF-532, PF-533, PF-534, PF-535, PF-536,PF-537, PF-538, PF-539, PF-540, PF-541, PF-542, PF- 543, PF-544, PF-546,PF-548, PF-553, PF-555, PF-556, PF-558, PF-560, PF-562, PF-563, PF-566,PF-567, PF-572, PF-573, PF-575, PF-576, PF- 577, PF-578, PF-580, PF-581,PF-583, PF-585, PF-585, PF-586, PF-587, PF-589, PF-591, PF-592, PF-595,PF-596, PF-598, PF-599, PF-600, PF- 603, PF-605, PF-606, PF-607, PF-609,PF-610, PF-612, PF-614, PF-615, PF-617, PF-618, PF-619, PF-621, PF-622,PF-623, PF-624, PF-625, PF- 626, PF-627, PF-629, PF-631, PF-632, PF-634,PF-635, PF-636, PF-637, PF-638, PF-639, PF-640, PF-643, PF-644, PF-645,PF-646, PF-647, PF- 651, PF-652, PF-653, PF-654, PF-655, PF-657, PF-658,PF-659, PF-660, PF-662, PF-663, PF-664, PF-665, PF-666, PF-667, PF-668,PF-670, PF- 672, PF-675, PF-677, PF-681, PF-682, PF-683, PF-684, PF-685,PF-686, PF-687, PF-688, PF-690, PF-691, PF-693, PF-694, PF-695, PF-696,PF- 697, PF-698, PF-699, PF-700, PF-702, PF-704, PF-737, PF-741, PF-744,PF-745, PF-746, PF-748, PF-749, PF-752, PF-756, PF-757, PF-760, PF- 761,PF-762, PF-763, PF-764, PF-770, PF-776, PF-S003 Gram Negative Bacteria:A. baumannii PF-531, PF-006, PF-538, PF-530 C. jejuni PF-006, PF-008,PF-033, PF-040, PF-053, PF-056, PF-057, PF-059, PF- 061, PF-063, PF-067,PF-068, PF-069, PF-071, PF-073, PF-140, PF-145, PF-148, PF-171, PF-175,PF-355, PF-356, PF-363, PF-366, PF-380, PF- 389, PF-390, PF-392, PF-393,PF-411, PF-418, PF-422, PF-425, PF-426, PF-431, PF-432, PF-456, PF-469,PF-470, PF-471, PF-472, PF-473, PF- 474, PF-475, PF-527, PF-548, PF-555,PF-556, PF-558, PF-559, PF-560, PF-562, PF-563, PF-564, PF-566, PF-567,PF-575, PF-576, PF-577, PF- 581, PF-584, PF-585, PF-586, PF-590, PF-591,PF-592, PF-595, PF-596, PF-598, PF-599, PF-601, PF-605, PF-607, PF-609,PF-610, PF-614, PF- 615, PF-S003 E. coli PF-007, PF-040, PF-053, PF-057,PF-068, PF-178, PF-344, PF-347, PF- 349, PF-350, PF-355, PF-360, PF-362,PF-363, PF-366, PF-369, PF-370, PF-374, PF-375, PF-376, PF-379, PF-380,PF-381, PF-383, PF-385, PF- 386, PF-387, PF-390, PF-395, PF-396, PF-398,PF-399, PF-401, PF-403, PF-410, PF-411, PF-413, PF-418, PF-425, PF-426,PF-427, PF-432, PF- 439, PF-440, PF-443, PF-444, PF-451, PF-452, PF-453,PF-454, PF-460, PF-469, PF-471, PF-473, PF-474, PF-478, PF-480, PF-514,PF-518, PF- 519, PF-524, PF-526, PF-528, PF-530, PF-531, PF-532, PF-533,PF-534, PF-536, PF-540, PF-541, PF-543, PF-546, PF-576, PF-577, PF-578,PF- 584, PF-586, PF-592, PF-595, PF-596, PF-598, PF-600, PF-603, PF-605,PF-606, PF-610, PF-612, PF-615, PF-619, PF-624, PF-634, PF-741, PF- 746,PF-761, PF-770, PF-776 F. nucleatum PF-C055, PF-C061, PF-C062, PF-C064,PF-C065, PF-C069, PF-C071, PF-C072, PF-C075, PF-C084, PF-C086, PF-C088,PF-C091, PF-C095, PF-C098, PF-C120, PF-C131, PF-C135, PF-C136, PF-C137,PF-C143, PF-C145, PF-C181, PF-C194, PF-C214, PF-C291, PF-C293 M. xanthusG-5, G-6, G-7 P. aeruginosa PF-053, PF-063, PF-067, PF-128, PF-140,PF-143, PF-168, PF-204, PF- 209, PF-355, PF-356, PF-366, PF-380, PF-411,PF-425, PF-432, PF-454, PF-458, PF-471, PF-474, PF-527, PF-531, PF-535,PF-536, PF-575, PF- 577, PF-605, PF-746, PF-761, PF-S003 P. gingivalisPF-C052, PF-C072, PF-C075, PF-C084, PF-C088, PF-C089, PF-C136, PF-C180,PF-C194, C293 P. mirabilis PF-040, PF-578, PF-612, PF-624, PF-634,PF-741, PF-770 Yeast Fungi: A. niger PF-531, PF-527, PF-672, PF-545,PF-168, PF-448, PF-525, PF-529, PF- 148 C. albicans PF-053, PF-056,PF-057, PF-071, PF-140, PF-148, PF-175, PF-278, PF- 307, PF-425, PF-426,PF-474, PF-475, PF-526, PF-527, PF-528, PF-545, PF-605, PF-606, PF-617,PF-627, PF-632, PF-635, PF-636, PF-639, PF- 640, PF-645, PF-646, PF-647,PF-654, PF-668, PF-672, PF-684, PF-686, PF-697, PF-698, PF-S003 T.rubrum PF-283, PF-307, PF-527, PF-531, PF-547, PF-672

In certain embodiments the activity against a particular microorganismor group of microorganisms can be increased by increasing the number ofpeptides or peptide domains with activity against that microorganism orgroup of microorganisms.

Thus, for example, in certain embodiments, a peptide or compositioneffective to kill or inhibit the growth and/or proliferation of a yeastor fungus can comprise or more peptides and/or one or more peptidedomains having sequences selected from the sequences shown in Tables 4,5, or 6 (e.g., PF-S003, PF-053, PF-056, PF-057, PF-071, PF-140, PF-148,PF-168, PF-175, PF-278, PF-283, PF-307, PF-425, PF-426, PF-448, PF-474,PF-475, PF-525, PF-526, PF-527, PF-528, PF-529, PF-531, PF-545, PF-547,PF-606, PF-617, PF-627, PF-632, PF-635, PF-636, PF-639, PF-640, PF-645,PF-646, PF-647, PF-654, PF-668, PF-672, PF-684, PF-686, PF-697, andPF-69)8. A peptide or composition effective to kill or inhibit thegrowth and/or proliferation of Aspergillus niger can comprise one ormore peptides and/or one or more peptide domains having sequencesselected from the group consisting of PF-531, PF-527, PF-672, PF-545,PF-168, PF-448, PF-525, PF-529, and PF-148. A peptide or compositioneffective to kill or inhibit the growth and/or proliferation of Candidaalbicans can comprise one or more peptides and/or one or more peptidedomains having sequences selected from the group consisting of PF-053,PF-056, PF-057, PF-071, PF-140, PF-148, PF-175, PF-278, PF-307, PF-425,PF-426, PF-474, PF-475, PF-526, PF-527, PF-528, PF-545, PF-605, PF-606,PF-617, PF-627, PF-632, PF-635, PF-636, PF-639, PF-640, PF-645, PF-646,PF-647, PF-654, PF-668, PF-672, PF-684, PF-686, PF-697, PF-698, andPF-S003. A peptide or composition effective to kill or inhibit thegrowth and/or proliferation of Trichophyton rubrum can comprise one ormore peptides and/or one or more peptide domains having sequencesselected from the group consisting of PF-283, PF-307, PF-527, PF-531,PF-547, and PF-672.

In certain embodiments a peptide or composition effective to kill orinhibit the growth and/or proliferation of a bacterium can comprise oneor more peptides and/or one or more peptide domains comprising orconsisting of sequences identified as having activity against abacterium in Tables 4, 5, or 6.

In certain embodiments a peptide or composition effective to kill orinhibit the growth and/or proliferation of a gram positive bacterium cancomprise one or more peptides and/or one or more peptide domainscomprising or consisting of sequences identified as having activityagainst a gram positive bacterium in Tables 4, 5, or 6. In certainembodiments a peptide or composition effective to kill or inhibit thegrowth and/or proliferation of a gram negative bacterium can compriseone or more peptides and/or one or more peptide domains comprising orconsisting of sequences identified as having activity against a gramnegative bacterium in Tables 4, 5, or 6.

In certain embodiments a peptide or composition effective to kill orinhibit the growth and/or proliferation of A. naeslundii can compriseone or more peptides and/or one or more peptide domains comprising orconsisting of sequences identified as having activity against A.Naeslundii in Tables 4, 5, or 6 (e.g., from the group consisting ofPF-531, PF-527, PF-672, PF-545, PF-168, PF-448, PF-525, PF-529, andPF-148).

In certain embodiments a peptide or composition effective to kill orinhibit the growth and/or proliferation of B. subtilis can comprise oneor more peptides and/or one or more peptide domains comprising orconsisting of sequences identified as having activity against B.subtilis in Tables 4, 5, or 6 (e.g., from the group consisting ofPF-002, PF-005, PF-006, PF-040, PF-053, PF-056, PF-061, PF-063, PF-067,PF-068, PF-069, PF-070, PF-071, PF-145, PF-148, PF-171, PF-175, PF-283,PF-289, PF-292, PF-296, PF-297, PF-301, PF-303, PF-305, PF-306, PF-307,PF-318, PF-319, PF-322, PF-335, PF-339, PF-342, PF-497, PF-499, PF-527,PF-531, PF-545, PF-547, PF-548, PF-549, PF-550, PF-552, PF-553, PF-554,PF-556, PF-557, PF-558, PF-559, PF-560, PF-561, PF-563, PF-564, PF-565,PF-566, PF-569, PF-571, PF-572, PF-574, PF-632, PF-636, PF-655, PF-659,PF-668, PF-670, PF-672, PF-686, PF-998, and PF-2003).

In certain embodiments a peptide or composition effective to kill orinhibit the growth and/or proliferation of C. difficile can comprise oneor more peptides and/or one or more peptide domains comprising orconsisting of sequences identified as having activity against C.difficile in Tables 4, 5, or 6 (e.g., from the group consisting ofPF-522, PF-531, and PF-538).

In certain embodiments a peptide or composition effective to kill orinhibit the growth and/or proliferation of C. jeikeium can comprise oneor more peptides and/or one or more peptide domains comprising orconsisting of sequences identified as having activity against C.jeikeium in Tables 4, 5, or 6 (e.g., from the group consisting ofPF-001, PF-003, PF-004, PF-101, PF-011, PF-012, PF-013, PF-021, PF-022,PF-025, PF-028, PF-030, PF-032, PF-033, PF-036, PF-037, PF-040, PF-042,PF-043, PF-046, PF-048, PF-052, PF-053, PF-056, PF-057, PF-063, PF-065,PF-067, PF-068, PF-073, PF-075, PF-076, PF-099, PF-124, PF-127, PF-129,PF-133, PF-135, PF-137, PF-139, PF-140, PF-145, PF-148, PF-164, PF-173,PF-176, PF-186, PF-188, PF-190, PF-191, PF-196, PF-199, PF-203, PF-204,PF-208, PF-527, PF-531, PF-545, PF-546, PF-548, PF-553, PF-556, PF-564,PF-566, PF-567, PF-575, PF-622, PF-523, PF-629, PF-632, PF-635, PF-637,PF-657, PF-668, PF-672, PF-681, PF-685, and PF-S003).

In certain embodiments a peptide or composition effective to kill orinhibit the growth and/or proliferation of E. faecalis can comprise oneor more peptides and/or one or more peptide domains comprising orconsisting of sequences identified as having activity against E.faecalis in Tables 4, 5, or 6 (e.g., from the group consisting ofPF-007, PF-053, PF-057, PF-068, PF-347, PF-349, PF-355, PF-356, PF-363,PF-366, PF-369, PF-374, PF-375, PF-376, PF-379, PF-380, PF-381, PF-386,PF-387, PF-389, PF-390, PF-392, PF-393, PF-394, PF-396, PF-398, PF-399,PF-401, PF-407, PF-410, PF-411, PF-418, PF-422, PF-425, PF-426, PF-427,PF-429, PF-431, PF-432, PF-439, PF-440, PF-444, PF-447, PF-450, PF-451,PF-452, PF-454, PF-456, PF-460, PF-461, PF-469, PF-470, PF-471, PF-472,PF-473, PF-474, PF-475, PF-480, PF-484, PF-514, PF-518, PF-519, PF-524,PF-530, PF-532, PF-533, PF-534, PF-536, PF-544, PF-545, PF-546, PF-547,PF-556, PF-577, PF-581, PF-582, PF-584, PF-585, PF-586, PF-588, PF-591,PF-592, PF-593, PF-594, PF-595, PF-596, PF-597, PF-598, PF-599, PF-601,PF-602, PF-604, PF-605, PF-607, PF-609, PF-610, PF-613, PF-614, PF-615,PF-616, PF-617, PF-618, PF-621, PF-622, PF-623, PF-627, PF-629, PF-631,PF-632, PF-635, PF-636, PF-637, PF-638, PF-639, PF-640, PF-643, PF-649,PF-657, PF-664, PF-667, PF-668, PF-672, PF-675, PF-677, PF-681, PF-684,PF-685, PF-686, PF-690, PF-695, and PF-698).

In certain embodiments a peptide or composition effective to kill orinhibit the growth and/or proliferation of M. luteus can comprise one ormore peptides and/or one or more peptide domains comprising orconsisting of sequences identified as having activity against M. luteusin Tables 4, 5, or 6 (e.g., from the group consisting of PF-001, PF-003,PF-004, PF-006, PF-007, PF-010, PF-012, PF-013, PF-020, PF-021, PF-022,PF-025, PF-030, PF-036, PF-037, PF-040, PF-042, PF-043, PF-051, PF-052,PF-053, PF-056, PF-057, PF-063, PF-067, PF-068, PF-071, PF-073, PF-075,PF-076, PF-125, PF-127, PF-137, PF-139, PF-140, PF-145, PF-148, PF-171,PF-175, PF-176, PF-199, PF-204, PF-212, PF-215, PF-224, PF-226, PF-234,PF-235, PF-249, PF-250, PF-255, PF-257, PF-264, PF-270, PF-271, PF-274,PF-276, PF-278, PF-357, PF-527, PF-543, PF-548, PF-556, PF-562, PF-566,PF-567, PF-578, PF-580, PF-600, PF-603, PF-612, PF-624, PF-634, PF-741,PF-745, PF-746, PF-761, PF-763, PF-770, PF-776, and PF-S003).

In certain embodiments a peptide or composition effective to kill orinhibit the growth and/or proliferation of MRSA can comprise one or morepeptides and/or one or more peptide domains comprising or consisting ofsequences identified as having activity against MRSA in Tables 4, 5, or6 (e.g., from the group consisting of PF-001, PF-003, PF-004, PF-006,PF-007, PF-010, PF-011, PF-012, PF-013, PF-015, PF-017, PF-019, PF-020,PF-021, PF-022, PF-023, PF-024, PF-025, PF-026, PF-027, PF-028, PF-029,PF-030, PF-031, PF-033, PF-035, PF-036, PF-037, PF-040, PF-041, PF-042,PF-043, PF-045, PF-046, PF-048, PF-049, PF-051, PF-052, PF-053, PF-056,PF-057, PF-058, PF-063, PF-064, PF-065, PF-066, PF-067, PF-068, PF-071,PF-073, PF-074, PF-075, PF-076, PF-140, PF-145, PF-148, PF-149, PF-156,PF-168, PF-171, PF-178, PF-191, PF-209, PF-347, PF-349, PF-350, PF-354,PF-355, PF-356, PF-357, PF-360, PF-362, PF-366, PF-369, PF-370, PF-373,PF-374, PF-375, PF-376, PF-378, PF-379, PF-380, PF-381, PF-382, PF-386,PF-387, PF-389, PF-390, PF-392, PF-393, PF-394, PF-395, PF-396, PF-398,PF-399, PF-401, PF-403, PF-404, PF-405, PF-406, PF-407, PF-408, PF-410,PF-411, PF-413, PF-417, PF-418, PF-422, PF-425, PF-426, PF-427, PF-429,PF-430, PF-431, PF-432, PF-439, PF-440, PF-442, PF-443, PF-444, PF-447,PF-450, PF-451, PF-452, PF-453, PF-454, PF-458, PF-460, PF-461, PF-469,PF-471, PF-472, PF-473, PF-474, PF-475, PF-478, PF-480, PF-518, PF-519,PF-524, PF-526, PF-527, PF-528, PF-530, PF-532, PF-533, PF-534, PF-536,PF-539, PF-540, PF-543, PF-544, PF-545, PF-546, PF-547, PF-548, PF-549,PF-551, PF-553, PF-555, PF-556, PF-558, PF-560, PF-561, PF-562, PF-564,PF-565, PF-566, PF-567, PF-576, PF-577, PF-578, PF-580, PF-581, PF-583,PF-584, PF-585, PF-586, PF-589, PF-592, PF-595, PF-596, PF-598, PF-599,PF-600, PF-603, PF-605, PF-606, PF-607, PF-609, PF-610, PF-612, PF-613,PF-615, PF-619, PF-622, PF-623, PF-624, PF-627, PF-629, PF-630, PF-632,PF-634, PF-635, PF-637, PF-638, PF-639, PF-652, PF-643, PF-654, PF-655,PF-656, PF-657, PF-658, PF-659, PF-661, PF-664, PF-667, PF-778, PF-672,PF-677, PF-680, PF-683, PF-685, PF-686, PF-690, PF-692, PF-694, PF-695,PF-738, PF-741, PF-745, PF-746, PF-760, PF-761, PF-763, PF-764, PF-770,PF-776, and PF-S003).

In certain embodiments a peptide or composition effective to kill orinhibit the growth and/or proliferation of S. epidermidis can compriseone or more peptides and/or one or more peptide domains comprising orconsisting of sequences identified as having activity against of S.epidermidis in Tables 4, 5, or 6 (e.g., from the group consisting ofPF-001, PF-003, PF-004, PF-006, PF-007, PF-009, PF-010, PF-012, PF-013,PF-020, PF-021, PF-022, PF-024, PF-025, PF-027, PF-028, PF-030, PF-032,PF-033, PF-034, PF-036, PF-037, PF-040, PF-041, PF-042, PF-043, PF-046,PF-048, PF-051, PF-052, PF-953, PF-956, PF-957, PF-961, PF-963, PF-964,PF-965, PF-967, PF-968, PF-971, PF-073, PF-074, PF-075, PF-076, PF-099,PF-123, PF-124, PF-125, PF-127, PF-128, PF-129, PF-137, PF-139, PF-140,PF-145, PF-148, PF-153, PF-157, PF-171, PF-173, PF-176, PF-178, PF-180,PF-186, PF-190, PF-191, PF-192, PF-196, PF-199, PF-203, PF-204, PF-208,PF-209, PF-226, PF-233, PF-273, PF-278, PF-283, PF-290, PF-292, PF-293,PF-294, PF-296, PF-297, PF-301, PF-307, PF-310, PF-313, PF-318, PF-319,PF-322, PF-335, PF-339, PF-342, PF-347, PF-349, PF-350, PF-355, PF-356,PF-357, PF-360, PF-363, PF-366, PF-369, PF-370, PF-373, PF-374, PF-375,PF-376, PF-378, PF-379, PF-380, PF-381, PF-383, PF-386, PF-387, PF-389,PF-390, PF-393, PF-395, PF-396, PF-397, PF-398, PF-399, PF-401, PF-403,PF-404, PF-406, PF-407, PF-408, PF-410, PF-411, PF-413, PF-417, PF-418,PF-422, PF-425, PF-246, PF-249, PF-430, PF-431, PF-432, PF-439, PF-440,PF-444, PF-447, PF-451, PF-452, PF-453, PF-454, PF-460, PF-469, PF-471,PF-473, PF-474, PF-475, PF-478, PF-480, PF-514, PF-518, PF-526, PF-527,PF-528, PF-530, PF-531, PF-533, PF-534, PF-536, PF-540, PF-543, PF-544,PF-546, PF-547, PF-548, PF-556, PF-558, PF-562, PF-576, PF-577, PF-578,PF-580, PF-583, PF-584, PF-585, PF-586, PF-592, PF-595, PF-596, PF-598,PF-599, PF-600, PF-603, PF-605, PF-606, PF-607, PF-610, PF-612, PF-613,PF-614, PF-615, PF-616, PF-619, PF-622, PF-623, PF-624, PF-627, PF-632,PF-634, PF-635, PF-637, PF-638, PF-655, PF-657, PF-659, PF-664, PF-667,PF-778, PF-672, PF-677, PF-681, PF-683, PF-685, PF-686, PF-690, PF-741,PF-746, PF-760, PF-761, PF-763, PF-770, PF-776, and PF-S003).

In certain embodiments a peptide or composition effective to kill orinhibit the growth and/or proliferation of S. mutans can comprise one ormore peptides and/or one or more peptide domains comprising orconsisting of sequences identified as having activity against S. mutansin Tables 4, 5, or 6 (e.g., from the group consisting of G-1, G-2, G-4,G-8, PF-020, PF-040, PF-051, PF-531, PF-543, PF-547, PF-578, PF-583,PF-600, PF-606, PF-612, PF-624, PF-634, PF-741, PF-745, PF-746, PF-761,PF-770, PF-776, PF-0055, PF-0057, PF-0058, PF-0061, PF-0062, PF-0072,PF-0075, PF-0084, PF-0085, PF-0088, PF-0098, PF-C131, PF-C135, PF-C139,PF-C142, PF-C146, PF-C180, PF-C194, PF-C281, PF-C290, PF-C291, PF-C293

In certain embodiments a peptide or composition effective to kill orinhibit the growth and/or proliferation of S. pneumoniae can compriseone or more peptides and/or one or more peptide domains comprising orconsisting of sequences identified as having activity against S.pneumoniae in Tables 4, 5, or 6 (e.g., from the group consisting ofPF-002, PF-005, PF-006, PF-020, PF-033, PF-040, PF-051, PF-053, PF-056,PF-057, PF-061, PF-063, PF-068, PF-071, PF-073, PF-140, PF-144, PF-145,PF-148, PF-171, PF-175, PF-178, PF-220, PF-355, PF-356, PF-357, PF-363,PF-366, PF-380, PF-389, PF-390, PF-393, PF-407, PF-411, PF-414, PF-415,PF-416, PF-417, PF-418, PF-419, PF-421, PF-422, PF-423, PF-424, PF-425,PF-426, PF-427, PF-428, PF-429, PF-430, PF-431, PF-432, PF-433, PF-434,PF-437, PF-439, PF-440, PF-442, PF-443, PF-444, PF-445, PF-446, PF-447,PF-448, PF-449, PF-450, PF-451, PF-452, PF-453, PF-454, PF-455, PF-457,PF-458, PF-469, PF-460, PF-461, PF-462, PF-464, PF-465, PF-466, PF-467,PF-468, PF-469, PF-471, PF-472, PF-473, PF-474, PF-475, PF-476, PF-477,PF-478, PF-479, PF-480, PF-482, PF-485, PF-511, PF-512, PF-513, PF-514,PF-515, PF-516, PF-517, PF-518, PF-519, PF-520, PF-521, PF-522, PF-523,PF-524, PF-525, PF-526, PF-527, PF-528, PF-529, PF-530, PF-531, PF-532,PF-533, PF-534, PF-535, PF-536, PF-537, PF-538, PF-539, PF-540, PF-541,PF-542, PF-543, PF-544, PF-546, PF-548, PF-553, PF-555, PF-556, PF-558,PF-560, PF-562, PF-563, PF-566, PF-567, PF-572, PF-573, PF-575, PF-576,PF-577, PF-578, PF-580, PF-581, PF-583, PF-585, PF-585, PF-586, PF-587,PF-589, PF-591, PF-592, PF-595, PF-596, PF-598, PF-599, PF-600, PF-603,PF-605, PF-606, PF-607, PF-609, PF-610, PF-612, PF-614, PF-615, PF-617,PF-618, PF-619, PF-621, PF-622, PF-623, PF-624, PF-625, PF-626, PF-627,PF-629, PF-631, PF-632, PF-634, PF-635, PF-636, PF-637, PF-638, PF-639,PF-640, PF-643, PF-644, PF-645, PF-646, PF-647, PF-651, PF-652, PF-653,PF-654, PF-655, PF-657, PF-658, PF-659, PF-660, PF-662, PF-663, PF-664,PF-665, PF-666, PF-667, PF-668, PF-670, PF-672, PF-675, PF-677, PF-681,PF-682, PF-683, PF-684, PF-685, PF-686, PF-687, PF-688, PF-690, PF-691,PF-693, PF-694, PF-695, PF-696, PF-697, PF-698, PF-699, PF-700, PF-702,PF-704, PF-737, PF-741, PF-744, PF-745, PF-746, PF-748, PF-749, PF-752,PF-756, PF-757, PF-760, PF-761, PF-762, PF-763, PF-764, PF-770, PF-776,and PF-S003).

In certain embodiments a peptide or composition effective to kill orinhibit the growth and/or proliferation of A. baumannii can comprise oneor more peptides and/or one or more peptide domains comprising orconsisting of sequences identified as having activity against A.baumannii in Tables 4, 5, or 6 (e.g., from the group consisting ofPF-531, PF-006, PF-538, and PF-530).

In certain embodiments a peptide or composition effective to kill orinhibit the growth and/or proliferation of C. jejuni can comprise one ormore peptides and/or one or more peptide domains comprising orconsisting of sequences identified as having activity against C. jejuniin Tables 4, 5, or 6 (e.g., from the group consisting of PF-006, PF-008,PF-033, PF-040, PF-053, PF-056, PF-057, PF-059, PF-061, PF-063, PF-067,PF-068, PF-069, PF-071, PF-073, PF-140, PF-145, PF-148, PF-171, PF-175,PF-355, PF-356, PF-363, PF-366, PF-380, PF-389, PF-390, PF-392, PF-393,PF-411, PF-418, PF-422, PF-425, PF-426, PF-431, PF-432, PF-456, PF-469,PF-470, PF-471, PF-472, PF-473, PF-474, PF-475, PF-527, PF-548, PF-555,PF-556, PF-558, PF-559, PF-560, PF-562, PF-563, PF-564, PF-566, PF-567,PF-575, PF-576, PF-577, PF-581, PF-584, PF-585, PF-586, PF-590, PF-591,PF-592, PF-595, PF-596, PF-598, PF-599, PF-601, PF-605, PF-607, PF-609,PF-610, PF-614, PF-615, and PF-S003).

In certain embodiments a peptide or composition effective to kill orinhibit the growth and/or proliferation of E. coli can comprise one ormore peptides and/or one or more peptide domains comprising orconsisting of sequences identified as having activity against E. coli inTables 4, 5, or 6 (e.g., from the group consisting of PF-007, PF-040,PF-053, PF-057, PF-068, PF-178, PF-344, PF-347, PF-349, PF-350, PF-355,PF-360, PF-362, PF-363, PF-366, PF-369, PF-370, PF-374, PF-375, PF-376,PF-379, PF-380, PF-381, PF-383, PF-385, PF-386, PF-387, PF-390, PF-395,PF-396, PF-398, PF-399, PF-401, PF-403, PF-410, PF-411, PF-413, PF-418,PF-425, PF-426, PF-427, PF-432, PF-439, PF-440, PF-443, PF-444, PF-451,PF-452, PF-453, PF-454, PF-460, PF-469, PF-471, PF-473, PF-474, PF-478,PF-480, PF-514, PF-518, PF-519, PF-524, PF-526, PF-528, PF-530, PF-531,PF-532, PF-533, PF-534, PF-536, PF-540, PF-541, PF-543, PF-546, PF-576,PF-577, PF-578, PF-584, PF-586, PF-592, PF-595, PF-596, PF-598, PF-600,PF-603, PF-605, PF-606, PF-610, PF-612, PF-615, PF-619, PF-624, PF-634,PF-741, PF-746, PF-761, PF-770, and PF-776).

In certain embodiments a peptide or composition effective to kill orinhibit the growth and/or proliferation of F. nucleatum can comprise oneor more peptides and/or one or more peptide domains comprising orconsisting of sequences identified as having activity against F.nucleatum in Tables 4, 5, or 6 (e.g., from the group consisting ofPF-C055, PF-0061, PF-0062, PF-0064, PF-0065, PF-0069, PF-0071, PF-0072,PF-0075, PF-C084, PF-0086, PF-0088, PF-0091, PF-0095, PF-0098, PF-C120,PF-C131, PF-C135, PF-C136, PF-C137, PF-C143, PF-C145, PF-C181, PF-C194,PF-C214, PF-C291, and PF-C293).

In certain embodiments a peptide or composition effective to kill orinhibit the growth and/or proliferation of M. Xanthus can comprise oneor more peptides and/or one or more peptide domains comprising orconsisting of sequences identified as having activity against M. Xanthusin Tables 4, 5, or 6 (e.g., from the group consisting of G-5, G-6, andG-7).

In certain embodiments a peptide or composition effective to kill orinhibit the growth and/or proliferation of P. aeruginosa can compriseone or more peptides and/or one or more peptide domains comprising orconsisting of sequences identified as having activity against P.aeruginosa in Tables 4, 5, or 6 (e.g., from the group consisting ofPF-053, PF-063, PF-067, PF-128, PF-140, PF-143, PF-168, PF-204, PF-209,PF-355, PF-356, PF-366, PF-380, PF-411, PF-425, PF-432, PF-454, PF-458,PF-471, PF-474, PF-527, PF-531, PF-535, PF-536, PF-575, PF-577, PF-605,PF-746, PF-761, and PF-S003).

In certain embodiments a peptide or composition effective to kill orinhibit the growth and/or proliferation of P. gingivalis can compriseone or more peptides and/or one or more peptide domains comprising orconsisting of sequences identified as having activity against P.gingivalis in Tables 4, 5, or 6 (e.g., from the group consisting ofPF-C052, PF-0072, PF-0075, PF-0084, PF-0088, PF-0089, PF-C136, PF-C180,PF-C194, and C293).

In certain embodiments a peptide or composition effective to kill orinhibit the growth and/or proliferation of P. mirabilis can comprise oneor more peptides and/or one or more peptide domains comprising orconsisting of sequences identified as having activity against P.mirabilis in Tables 4, 5, or 6 (e.g., from the group consisting ofPF-040, PF-578, PF-612, PF-624, PF-634, PF-741, and PF-770).

It was also a surprising discovery that a number of novel antimicrobialpeptides are characterized by the presence of particular amino acidmotifs. Such motifs include KIF, FIK, KIH, HIK, and KIV, as illustratedin Table 7.

TABLE 7 Antimicrobial peptides characterized by particular motifs. SEQID Motif Omnibus # Sequence NO KIF PF-278 LSLATFA KIF MTRSNWSLKRFNRL1567 PF-C059 QKIIDMSKFLFSLILFIMIVVIYIGKSIGGYSAIVSS 1568 IMLELDTVLYNK KIFFIYK PF-C073 FESLLPQATKKIVNNKGSKIN KIF 1569 PF-C085 KKF KIFVIINWFYHKYIILNFEENF 1570 PF-531 YIQFHLNQQPRPKVKKI KIF L 1571 PF-C194NTNDLLQAFELMGLGMAGVFIVLGILYIVAELLI 1572 KIF PVNN PF-C201IFKLFEEHLLYLLDAFYYS KIF RRLKQGLYRRKE 1573 QPYTQDLFRM PF-442 MQIFYIKT KIFLSFFLFLLIFSQCFYKIEE 1574 PF-C252 NYRLVNAIFS KIF KKKFIKF 1575 FIK PF-251MAWK FIK LDKVVSQKECNNFLEKEENKKLLKL 1576 LRIQKNMR PF-261 MDIWK FIKSFNTVNTYLLLSCVLLIILVLYFYVI 1577 NPA PF-497 LVLRICTDLFT FIK WTIKQRKS 1578PF-775 DLCGQE FIK FKTCVTNQLAKK 1579 PF-591 DLLKSLLGQDGAKNDEIIE FIK IIMEK1580 PF-597 DEIKVSDEEIEK FIK ENNL 1581 PF-608 LICEVVKPEED FIKVKLNEDNVTAKISREFIAKKI 1582 DA IT-133 Y FIK DDNEALSKDWEVIGNDLKGTIDKYGKEFK1583 VR PF-C252 NYRLVNAIFSKIFKKK FIK F 1584 PF-C278 DMKIIKLYIKILSFL FIKYCNKKLNSVKLKA 1585 PF-C290 GNVHPESDFHNLIQ FIK TFLYFTIFFKYFL 1586 PF-006MGIIAGIIK FIK GLIEKFTGK 1587 PF-013 LIQKGLNQTFIVVIRLNN FIK KS 1588PF-040 MIHLTKQNTMEALH FIK QFYDMFFILNFNV 1589 KIH PF-252MKKLVAALAVIVILTGCVYDPVNYD KIH DQEF 1590 QDHLRQNG PF-575 LNFRAENKILE KIHISLIDTVEGSA 1591 PF-533 KTPND KIH KTIIIKHIIL 1592 HIK PF-222 HIK ETR1593 PF-319 SIGSMIGMYSFRHKTK HIK FTFGIPFILFLQFLLV 1594 YFYILK PF-477HKNKLNIP HIK S 1595 KIV PF-272 MTLTIKIKHRS KIV PLNLISLVYAFFTYNFVANRI1596 MFLTND PF-758 PEII KIV SGLL 1597 PF-336 MLTSRKKRLK KIV EEQNKKDESI1598 PF-C073 FESLLPQATK KIV NNKGSKINKIF 1599 PF-721 TEQAK KIV DILNNWLE1600 PF-730 FEDIEQIIKYHLIDG KIV APLLLDR 1601 PF-095 KRGS KIVIAIAVVLIVLAGVWVW 1602 PF-028 ALDCSEQSVILWYETILD KIV GVIK 1603 VIK PF-257VWENRKKYLENEIERHNVFLKLGQE VIK GLNA 1604 LASRGR PF-226LMFFSENMDKRDTLSGKFRYFAGSK VIK LMNW 1605 LSENGK PF-580 EILNNNQ VIKELTMKYKTQFESNLGGWTARARR 1606 PF-366 ALCS VIK AIELGIINVHLQ 1607 PF-C092NGDKKAKEELDKWDE VIK ELNIQF 1608 PF-S028 GS VIKKRRKRMSKKKHRKMLRRTRVQRRKLGK 1609 PF-103 VIK ISVPGQVQMLIP 1610 PF-527 GSVIK KRRKRMAKKKHRKLLKKTRIQRRRAGK 1611 PF-167 AIEG VIK KGACFKLLRHEMF 1612PF-C166 KRKHENVIVAEEMR VIK N 1613 PF-007 MGIIAGIIK VIK SLIEQFTGK 1614PF-071 HCVIGNVVDIANLLKRRAVYRDIAD VIK MR 1615 PF-028ALDCSEQSVILWYETILDKIVG VIK 1616 PRP PF-C031 WSESQPPTAT PRPHAEVARAGLVTPPTL 1617 PF-752 LHVIR PRP ELSELKFPITKILKVNKQGLKK 1618 PF-672MRFGSLALVAYDSAIKHSW PRP SSVRRLRM 1619 PF-088 VMFVLTRGRS PRP MIPAY 1620PF-143 LS PRP IIVSRRSRADNNNDWSR 1621 PF-168 VLPFPAIPLSRRRACVAA PRPRSRQRAS 1622 PF-531 YIQFHLNQQ PRP KVKKIKIFL 1623 All groups areassociated with antimicrobial activity

In certain embodiments, peptides described herein can have multipleactivities. Thus for example, a peptide can have both binding/targetingactivity and antimicrobial activity. Illustrative peptides havingmultiple activities are shown in Table 8. Such peptides can be used,e.g., in a chimeric construct, for any or all of these properties. Thus,for example, a peptide designated “B” in Table 8 can be used as atargeting peptide. If it is also designated G or M it can also be usedfor antimicrobial activity.

TABLE 8 Peptides having multiple activities. Peptide Activities PeptideActivities Peptide Activities Peptide Activities PF-001 G B PF-224 G BPF-448 G B M PF-592 G B PF-002 G B PF-226 G B PF-450 G B PF-593 G BPF-003 G B PF-233 G B PF-451 G B PF-594 G B PF-004 G B PF-234 G B PF-452G B PF-595 G B PF-005 G B PF-235 G B PF-453 G B PF-596 G B PF-006 G B MPF-249 G B PF-454 G B PF-597 G B PF-007 G B PF-255 G B PF-456 G B PF-598G B PF-008 G B PF-257 G B PF-457 G B PF-599 G B PF-009 G B PF-270 G BPF-458 G B PF-600 G B M PF-010 G B PF-271 G B PF-459 G B PF-601 G BPF-011 G B PF-273 G B PF-460 G B PF-602 G B PF-012 G B PF-276 G B PF-461G B PF-603 G B PF-013 G B PF-278 G B M PF-462 G B PF-604 G B PF-015 G BPF-283 G B M PF-464 G B PF-605 G B PF-017 G B PF-289 G B PF-465 G BPF-606 G M PF-020 G B PF-292 G B PF-466 G B PF-607 G B PF-021 G B PF-294G B PF-467 G B PF-609 G B PF-022 G B PF-297 G B PF-469 G B PF-610 G BPF-023 G B PF-301 G B PF-470 G B PF-612 G B PF-024 G B PF-305 G B PF-471G B PF-613 G B PF-025 G B PF-306 G B PF-472 G B PF-614 G B PF-026 G BPF-307 G B M PF-473 G B PF-615 G B PF-027 G B PF-313 G B PF-474 G BPF-616 G B PF-028 G B PF-319 G B PF-475 G B PF-617 G B PF-029 G B PF-322G M PF-476 G B PF-619 G B PF-030 G B PF-344 G B PF-477 G B PF-621 G BPF-031 G B PF-347 G B PF-478 G B PF-622 G B PF-033 G B PF-349 G B PF-479G B PF-623 G B PF-034 G B PF-350 G B PF-480 G B PF-625 G B PF-035 G BPF-354 G B PF-482 G B PF-626 G B PF-036 G B PF-355 G B PF-484 G B PF-627G B PF-037 G B PF-356 G B PF-497 B M PF-629 G B PF-040 G B PF-357 G BPF-499 B M PF-630 G B PF-041 G B PF-360 G B PF-511 G B M PF-631 G BPF-042 G B PF-362 G B PF-512 G B M PF-632 G B PF-043 G B PF-363 G BPF-513 G B PF-634 G B PF-045 G B PF-366 G B PF-514 G B PF-635 G B PF-046G B PF-369 G B PF-515 G B PF-636 G B PF-048 G B PF-370 G B PF-516 GPF-637 G B PF-049 G B PF-373 G B PF-517 G B PF-638 G B PF-051 G B PF-374G B PF-518 G B PF-639 G B PF-052 G B PF-375 G B PF-519 G B PF-640 G BPF-053 G B PF-376 G B PF-520 G B M PF-642 G B PF-056 G B PF-378 G BPF-521 G B M PF-655 G B PF-057 G B PF-379 G B PF-522 G B M PF-664 G BPF-058 G B PF-380 G B PF-523 B M PF-672 G B M PF-061 G B PF-381 G BPF-524 G B M PF-681 G B PF-063 G B PF-382 G B PF-525 G M PF-686 G BPF-064 G B PF-383 G B PF-526 G B PF-737 G B PF-065 G B PF-385 G B PF-527G B M PF-738 G B PF-066 G B PF-386 G B PF-528 G B PF-741 G B PF-067 G BPF-387 G B PF-529 G B M PF-744 G B PF-068 G B PF-389 G B PF-530 G MPF-745 G B PF-069 G B PF-390 G B PF-531 G M PF-746 G B PF-070 G B PF-392G B PF-537 G B PF-748 G B PF-071 G B PF-393 G B PF-538 G M PF-749 G BPF-073 G B PF-394 G B PF-539 G B PF-752 G B PF-074 G B PF-395 G B PF-540G B PF-756 G B PF-075 G B PF-396 G B PF-542 G B PF-757 G B PF-076 G BPF-397 G B PF-543 G B PF-760 G B PF-099 G B PF-398 G B PF-544 G B PF-761G B PF-123 G B PF-399 G B PF-545 G B M PF-762 G B PF-124 G B PF-401 G BPF-546 G B PF-763 G B PF-125 G B PF-403 G B PF-547 G B M PF-764 G BPF-127 G B PF-404 G B PF-548 G B PF-770 G B PF-128 G B PF-405 G B PF-549G B PF-776 G B PF-129 G B PF-406 G B PF-550 G B PF-C052 G B PF-133 G BPF-407 G B PF-551 G B PF-C055 G B PF-135 G B PF-408 G B PF-552 G BPF-C057 G B PF-137 G B PF-410 G B PF-553 G B PF-C058 G B PF-139 G BPF-411 G B PF-554 G B PF-C061 G B PF-140 G B PF-413 G B PF-555 G BPF-C062 G B PF-143 G B PF-414 G B PF-556 G B PF-C064 G B PF-144 G BPF-416 G B PF-557 G B PF-C065 G B PF-145 G B PF-417 G B PF-558 G BPF-C069 G B PF-148 G B M PF-418 G B PF-559 G B PF-C071 G B PF-149 G BPF-421 G B PF-560 G B PF-C072 G B PF-153 G B PF-422 G B PF-562 G BPF-C075 G B PF-156 G B PF-423 G B PF-563 G B PF-C084 G B PF-157 G BPF-424 G B PF-564 G B PF-C085 G B PF-164 G B PF-425 G B PF-566 G BPF-C086 G B PF-168 G B M PF-426 G B PF-567 G B PF-C088 G B PF-171 G BPF-427 G B PF-569 G B PF-C091 G B PF-173 G B PF-428 G B PF-572 G BPF-C095 G B PF-175 G B PF-429 G B PF-573 G B PF-C098 G B PF-176 G BPF-430 G B PF-575 G B PF-C120 G B PF-178 G B PF-431 G B PF-576 G BPF-C131 G B PF-180 G B PF-432 G B PF-577 G B PF-C135 G B PF-186 G BPF-433 G B PF-578 G B PF-C136 G B PF-188 G B PF-434 G B PF-580 G BPF-C137 G B PF-190 G B PF-437 G M PF-581 G B PF-C139 G B PF-191 G BPF-439 G B PF-583 G B M PF-C142 G B PF-192 G B PF-440 G B PF-584 G BPF-C143 G B PF-196 G B PF-442 G B PF-585 G B PF-C145 G B PF-203 G BPF-443 G B PF-586 G B PF-C180 G B PF-204 G B PF-444 G B PF-587 G BPF-C181 G B PF-208 G B PF-445 G B PF-588 G B PF-C194 G B PF-209 G B MPF-446 G B PF-589 G B PF-C281 G B PF-212 G B PF-447 G B PF-590 G BPF-C290 G B PF-215 G B PF-S003 G B PF-C291 G B B: targeting/bindingactivity; M: antimicrobial activity; G: Growth or phenotype altering.

Other peptides believed to show binding, growth altering, and/orantimicrobial activity are shown in Table 9.

TABLE 9 Additional peptides believed to have binding, growth altering,and/or antimicrobial activity. ID Sequence SEQ ID No. PF-198RRLASRRSLVVST 1624 PF-227 RLLGLYGENSAAGFIASVIGAVIILFIYNLIARKS 1625PF-260 GHLRVCWILWLQSANPLSFRHHYLAVMW 1626 PF-261MDIWKFIKSFNTVNTYLLLSCVLLIILVLYFYVINPA 1627 PF-277MIIQNKKIEKIYKYQTKEIFLNKTSLRAGFVFRMVRVLI 1628 PF-280MLIDWQEPDIEKSFCAAFLKISVSVLVYRTPLGYGNQLRE 1629 PF-286 FFDGEVGCGC 1630PF-287 ILEQNIEEVFFIQS 1631 PF-312 MDKIRIWNNFHISNEYIKQRYGIISIPLFYVYLF1632 PF-321 FAKKNPCRMRVPNTGTWYLVVNQDGNSGIVNFSINTIQN 1633 PF-327MLVFQMRYQMRYVDKTSTVLKQTKNSDYADK 1634 PF-330MLMNFEVYQQRILIIYNKCYHLKAVGKNLQLFIIVD 1635 PF-331MGRHLWNPSYFVATVSENTEEQIRKYINNQKKQVK 1636 PF-341 DDKNEGKIAQGEY 1637PF-391 EASVYRE 1638 PF-420 MVKHNFDVTDKTGKISSKHCFEITDKTDVV 1639 PF-708DRPSQTTHHTLSSSRITGPS 1640 PF-710 EALLPPDPPDEDSQRIIPQ 1641 PF-713DRPSQTTHHTLSSSRITGPS 1642 PF-715 LEDTKALFPCFVPI 1643 PF-718KKYSSFKSMIDDLEYDA 1644 PF-719 FKSMIDDLEYDA 1645 PF-721 TEQAKKIVDILNNWLE1646 PF-722 STSPSVTSVYAEALGLK 1647 PF-723 VGAMAIFLNVVAMLAGV 1648 PF-725ARTIQNNGCLIHNSRYP 1649 PF-726 CDDLYALEAQGTLNELLKK 1650 PF-729 TPEPVVIVKP1651 PF-730 FEDIEQIIKYHLIDGKIVAPLLLDR 1652 PF-734SDIIAEMFQQGELEPMLRDAVAA 1653 PF-736 KGSASGSASGSGSAK 1654 PF-739KSGASSVASAAKSG 1655 PF-742 AAATTATTAK 1656 PF-743 TKGTTTGTAKTTGVTTGTAK1657 PF-769 GSRGGAKRGGARG 1658 PF- WSESQPPTATPRPHAEVARAGLVTPPTL 1659C031 PF- QPIGFPTDSVHGTDLVHRLRGTTSSR 1660 C038 PF-LENLDIEGLTEMKEHIEDLIAEKSAAESIEEVIVEAE 1661 C077 PF-AYSLTFQNPNDNLTDEEVAKYMEKITKALTEKIGAEVR 1662 C205 PF-S016PLTRETFAERGIRKARVARTFSEEEPPF 1663

III. Design and Construction of STAMPs and Other Chimeric Constructs.

In various embodiments this invention provides chimeric moietiescomprising one or more targeting moieties attached to one or moreeffectors. The targeting moieties can be selected to preferentially bindto a target microorganism (e.g., bacteria, virus, fungi, yeast, alga,protozoan, etc.) or group of microorganisms (e.g., gram-negative orgram-positive bacteria, particular genus, species, etc.) In certainembodiments the targeting moiety comprises one or more novelmicroorganism-binding peptides as described herein (see, e.g., Table 3,and/or Table 10, and/or Table 12). In certain embodiments the targetingmoiety comprises non-peptide moieties (e.g., antibodies, receptor,receptor ligand, lectin, and the like).

In various embodiments the effector comprises a moiety whose activity isto be delivered to the target microorganism(s), to a biofilm comprisingthe target microorganism(s), to a cell or tissue comprising the targetmicroorganism(s), and the like. In certain embodiments the targetingmoiety comprises one or more antimicrobial peptide(s) as describedherein (see, e.g., Tables 4, 5 and/or 14), an antibiotic (including, butnot limited to a steroid antibiotic), a detectable label, a porphyrin, aphotosensitizing agent, an epitope tag, a lipid or liposome, ananoparticle, a dendrimer, and the like.

In certain embodiments one or more targeting moieties are attached to asingle effector. In certain embodiments one or more effectors areattached to a single targeting moiety. In certain embodiments multipletargeting moieties are attached to multiple effectors. The targetingmoieties(s) can be attached directly to the effector(s) or through alinker. Where the targeting moiety and the effector comprise peptidesthe chimeric moiety can be a fusion protein.

A) Targeting Moieties.

In various embodiments this invention provides targeting moieties thatpreferentially and/or specifically bind to a microorganism (e.g., abacterium, a fungus, a yeast, etc.). One or more such targeting moietiescan be attached to one or more effectors to provide chimeric moietiesthat are capable of delivering the effector(s) to a target (e.g., abacterium, a fungus, a yeast, a biofilm comprising the bacterium orfungus or yeast, etc.).

In various embodiments, targeting moieties include, but are not limitedto peptides that preferentially bind particular microorganisms (e.g.,bacteria, fungi, yeasts, protozoa, algae, viruses, etc.) or groups ofsuch microorganisms, e.g., as described above, antibodies that bindparticular microorganisms or groups of microorganisms, receptor ligandsthat bind particular microorganisms or groups of microorganisms,porphyrins (e.g., metalloporphyrins), lectins that bind particularmicroorganisms or groups of microorganisms, and the like. As indicatedit will be appreciated that references to microorganisms or groups ofmicroorganism include bacteria or groups of bacteria, viruses or groupsof viruses, yeasts or groups of yeasts, protozoa or groups of protozoa,viruses or groups of viruses, and the like.

i. Targeting Peptides.

In certain embodiments, the targeting moiety comprises one or moretargeting peptides that bind particular bacteria, fungi, and/or yeasts,and/or algae, and/or viruses and/or that bind particular groups ofbacteria, and/or groups of fungi, and/or groups of yeasts, and/or groupsof algae.

In certain embodiments the targeting peptide can comprise one or moredomains capable of binding, specifically binding, or preferentiallybinding to a microorganism, e.g., a target microbial organism (see,e.g., Table 3). In certain embodiment, the targeting peptide beidentified via screening peptide libraries. For example, a phage displaypeptide library can be screened against a target microbial organism or adesired antigen or epitope thereof. Any peptide identified through suchscreening can be used as a targeting peptide for the target microbialorganism. Illustrative additional targeting peptides are shown in Table10.

TABLE 10 Additional illustrative targeting moieties. SEQ TargetingMoiety/ ID Organism Structure/sequence NO LPSB-1 RGLRRLGRRGLRRLGR 1664Phob-1 KPVLPVLPVLPVL 1665 LPSB-2 VLRIIRIAVLRIIRIA 1666 LPTG-1LPETGGSGGSLPETG 1667 α-1 RAHIRRAHIRR 1668 ANION-1 DEDEDDEEDDDEEE 1669PHILIC-1 STMCGSTMCGSTMCG 1670 SA5.1/S. aureus VRLPLWLPSLNE 1671 SA5.3/S.aureus ANYFLPPVLSSS 1672 SA5.4/S. aureus SHPWNAQRELSV 1673 SA5.5/S.aureus SVSVGMRPMPRP 1674 SA5.6/S. aureus WTPLHPSTNRPP 1675 SA5.7/S.aureus SVSVGMKPSPRP 1676 SA5.8/S. aureus SVSVGMKPSPRP 1677 SA5.9/S.aureus SVPVGPYNESQP 1678 SA5.10/S. aureus WAPPLFRSSLFY 1679 SA2.2/S.aureus WAPPXPXSSLFY 1680 SA2.4/S. aureus HHGWTHHWPPPP 1681 SA2.5/S.aureus SYYSLPPIFHIP 1682 SA2.6/S. aureus HFQENPLSRGGEL 1683 SA2.7/S.aureus FSYSPTRAPLNM 1684 SA2.8/S. aureus SXPXXMKXSXXX 1685 SA2.9/S.aureus VSRHQSWHPHDL 1686 SA2.10/S. aureus DYXYRGLPRXET 1687 SA2.11/S.aureus SVSVGMKPSPRP 1688 S. aureus/ConsensusV/Q/H-P/H-H-E-F/Y-K/H-H/A-L/H-X-X-K/R-P/L 1689 DH5.1/E coli.KHLQNRSTGYET 1690 DH5.2/E coli. HIHSLSPSKTWP 1691 DH5.3/E coli.TITPTDAEMPFL 1692 DH5.4/E coli. HLLESGVLERGM 1693 DH5.5/E coli.HDRYHIPPLQLH 1694 DH5.6/E coli. VNTLQNVRHMAA 1695 DH5.7/E coli.SNYMKLRAVSPF 1696 DH5.8/E coli. NLQMPYAWRTEF 1697 DH5.9/E coli.QKPLTGPHFSLI 1698 CSP/S. mutans SGSLSTFFRLFNRSFTQALGK 1699 CSPC18/S.mutans LSTFFRLFNRSFTQALGK 1700 CSPC16/S. mutans TFFRLFNRSFTQALGK 1701CSPM8/S. mutans TFFRLFNR 1702 KH/Pseudomonas spp KKHRKHRKHRKH 1703 (US2004/0137482) cCF10 LVTLVFV 1704 AgrD1 YSTCDFIM 1705 AgrD2 GVNACSSLF1706 AgrD3 YINCDFLL 1707 NisinA ITSISLCTPGCKTGALMGCNMRTATCIICSIIIVSK1708 PlnA KSSAYSLQMGATAIKQVKKLFKKWGW 1709 S3L1-5 WWYNWWQDW 1710Penetratin RQIKIWFWNRRMKWKK* 1711 Tat EHWSYCDLRPG 1712 Pep-1NKETWWETWWTEW 1713 Pep27 MRKEFHNVLSSGQLLADKRPARDYNRK 1714 HABP35LKQKIKHVVKLKVVVKLRSQLVKRKQN 1715 HABP42 (all D) STMMSRSHKTRSHHV 1716HABP52 GAHWQFNALTVRGGGS 1717 Hi3/17 KQRTSIRATEGCLPS 1718 α-E. colipeptide QEKIRVRLSA 1719 Salivary Receptor QLKTADLPAGRDETTSFVLV* 1720Adhesion Fragment S1 (Sushi frag.) GFKLKGMARISCLPNGQWSNFPPKCIRECAMVSS1721 (LPS binding) S3 (Sushi frag.) HAEHKVKIGVEQKYGQFPQGTEVTYTCSGNYFLM1722 (LPS binding) MArg.1 AMDMYSIEDRYFGGYAPEVG 1723 (Mycoplasma infectedcell line binding peptide BPI fragment 1 ASQQGTAALQKELKRIKPDYSDSFKIKH1724 (LPS binding) 6,376,462 BPI fragment 2SSQISMVPNVGLKFSISNANIKISGKWKAQKRFLK 1725 (LPS binding) 6,376,462 BPIfragment 3 VHVHISKSKVGWLIQLFHKKIESALRNK 1726 (LPS binding) 6,376,462 LBPfragment 1 AAQEGLLALQSELLRITLPDFTGDLRIPH 1727 (LPS binding) 6,376,462LBP fragment 2 HSALRPVPGQGLSLSISDSSIRVQGRWKVRKSFFK 1728 (LPS binding)6,376,462 LBP fragment 3 VEVDMSGDLGWLLNLFHNQIESKFQKV 1729 (LPS binding)6,376,462 B. anthracis spore ATYPLPIR 1730 binding (WO/1999/036081)Bacillus spore binding peptides of 5-12 amino acids containing thesequence 1731 (WO/1999/036081) Asn-His-Phe-Leu peptides of 5-12 aminoacids containing the sequence 1732 Asn-His-Phe-Leu-ProThr-Ser-Glu-Asn-Val-Arg-Thr (TSQNVRT) 1733 A peptide of formulaThr-Tyr-Pro-X-Pro-X-Arg 1734 (TYPXPXR) where X is a Ile, Val or Leu. Apeptide having the sequence TSQNVRT. 1735 A peptide having the sequenceTYPLPIR 1736 LPS binding peptide 1 TFRRLKWK 1737 (6,384,188) LPS BP 2(6,384,188) RWKVRKSFFKLQ 1738 LPS BP 3 (6,384,188) KWKAQKRFLKMS 1739Pseudomonas pilin KCTSDQDEQFIPKGCSK 1740 binding peptide (5,494,672)RNAII inhibiting YSPWTNF 1741 peptide (S. Aureus) Patents and patentpublications disclosing the referenced antibodies are identified in thetable.

In certain embodiments the targeting moieties can comprise otherentities, particularly when utilized with an antimicrobial peptide asdescribed, for example, in Table 4. Illustrative targeting moieties caninclude a polypeptide, a peptide, a small molecule, a ligand, areceptor, an antibody, a protein, or portions thereof that specificallyinteract with a target microbial organism, e.g., the cell surfaceappendages such as flagella and pili, and surface exposed proteins,lipids and polysaccharides of a target microbial organism.

ii. Targeting Antibodies.

In certain embodiments the targeting moieties can comprise one or moreantibodies that bind specifically or preferentially a microorganism orgroup of microorganisms (e.g., bacteria, fungi, yeasts, protozoa,viruses, algae, etc.). The antibodies are selected to bind an epitopecharacteristic or the particular target microorganism(s). In variousembodiments such epitopes or antigens are typically is gram-positive orgram-negative specific, or genus-specific, or species-specific, orstrain specific and located on the surface of a target microbialorganism. The antibody that binds the epitope or antigen can direct ananti-microbial peptide moiety or other effector to the site.Furthermore, in certain embodiments the antibody itself can provideanti-microbial activity in addition to the activity provided by effectormoiety since the antibody may engage an immune system effector (e.g., aT-cell) and thereby elicit an antibody-associated immune response, e.g.,a humoral immune response.

Antibodies that bind particular target microorganisms can be made usingany methods readily available to one skilled in the art. For example, asdescribed in U.S. Pat. No. 6,231,857 (incorporated herein by reference)three monoclonal antibodies, i.e., SWLA1, SWLA2, and SWLA3 have beenmade against S. mutans. Monoclonal antibodies obtained from non-humananimals to be used in a targeting moiety can also be humanized by anymeans available in the art to decrease their immunogenicity and increasetheir ability to elicit anti-microbial immune response of a human.Illustrative microorganisms and/or targets to which antibodies may bedirected are shown, for example, in Tables 3 and 11.

Various forms of antibody include, without limitation, whole antibodies,antibody fragments (e.g., (Fab′)₂ Fab′, etc.), single chain antibodies(e.g., scFv), minibodies, Di-miniantibody, Tetra-miniantibody, (scFv)₂,Diabody, scDiabody, Triabody, Tetrabody, Tandem diabody, VHH,nanobodies, affibodies, unibodies, and the like.

Methods of making such antibodies are well known to those of skill inthe art. In various embodiments, such methods typically involveproviding the microorganism, or a component thereof for use as anantigen to raise an immune response in an organism or for use in ascreening protocol (e.g., phage or yeast display).

For example, polyclonal antibodies are typically raised by one or moreinjections (e.g. subcutaneous or intramuscular injections) of the targetmicroorganism(s) or components thereof into a suitable non-human mammal(e.g., mouse, rabbit, rat, etc.).

If desired, the immunizing microorganism or antigen derived therefromcan be administered with or coupled to a carrier protein by conjugationusing techniques that are well-known in the art. Such commonly usedcarriers which are chemically coupled to the peptide include keyholelimpet hemocyanin (KLH), thyroglobulin, bovine serum albumin (BSA), andtetanus toxoid. The coupled peptide is then used to immunize the animal(e.g. a mouse or a rabbit).

The antibodies are then obtained from blood samples taken from themammal. The techniques used to develop polyclonal antibodies are knownin the art (see, e.g., Methods of Enzymology, “Production of AntiseraWith Small Doses of Immunogen: Multiple Intradermal Injections”,Langone, et al. eds. (Acad. Press, 1981)). Polyclonal antibodiesproduced by the animals can be further purified, for example, by bindingto and elution from a matrix to which the peptide to which theantibodies were raised is bound. Those of skill in the art will know ofvarious techniques common in the immunology arts for purification and/orconcentration of polyclonal antibodies, as well as monoclonal antibodiessee, for example, Coligan, et al. (1991) Unit 9, Current Protocols inImmunology, Wiley Interscience).

In certain embodiments the antibodies produced will be monoclonalantibodies (“mAb's”). The general method used for production ofhybridomas secreting mAbs is well known (Kohler and Milstein (1975)Nature, 256:495

Antibody fragments, e.g. single chain antibodies (scFv or others), canalso be produced/selected using phage display and/or yeast displaytechnology. The ability to express antibody fragments on the surface ofviruses that infect bacteria (bacteriophage or phage) or yeasts makes itpossible to isolate a single binding antibody fragment, e.g., from alibrary of greater than 10¹⁰ nonbinding clones. To express antibodyfragments on the surface of phage (phage display) or yeast, an antibodyfragment gene is inserted into the gene encoding a phage surface protein(e.g., pIII) and the antibody fragment-pIII fusion protein is displayedon the phage surface (McCafferty et al. (1990) Nature, 348: 552-554;Hoogenboom et al. (1991) Nucleic Acids Res. 19: 4133-4137).

Since the antibody fragments on the surface of the phage or yeast arefunctional, phage bearing antigen binding antibody fragments can beseparated from non-binding phage by antigen affinity chromatography(McCafferty et al. (1990) Nature, 348: 552-554). Depending on theaffinity of the antibody fragment, enrichment factors of 20fold—1,000,000 fold are obtained for a single round of affinityselection.

Human antibodies can be produced without prior immunization bydisplaying very large and diverse V-gene repertoires on phage (Marks etal. (1991) J. Mol. Biol. 222: 581-597.

In certain embodiments, nanobodies can be used as targeting moieties.Methods of making V_(h)H (nanobodies) are also well known to those ofskill in the art. The Camelidae heavy chain antibodies are found ashomodimers of a single heavy chain, dimerized via their constantregions. The variable domains of these camelidae heavy chain antibodiesare referred to as V_(HH) domains or V_(HH), and can be either used perse as nanobodies and/or as a starting point for obtaining nanobodies.Isolated V_(HH) retain the ability to bind antigen with high specificity(see, e.g., Hamers-Casterman et al. (1993) Nature 363: 446-448). Incertain embodiments such V_(HH) domains, or nucleotide sequencesencoding them, can be derived from antibodies raised in Camelidaespecies, for example in camel, dromedary, llama, alpaca and guanaco.Other species besides Camelidae (e.g. shark, pufferfish) can producefunctional antigen-binding heavy chain antibodies, from which(nucleotide sequences encoding) such naturally occurring V_(HH) can beobtained, e.g. using the methods described in U.S. Patent Publication US2006/0211088.

In various embodiments, for use in therapy, human proteins arepreferred, primarily because they are not as likely to provoke an immuneresponse when administered to a patient. Comparisons of camelid V_(HH)with the V_(H) domains of human antibodies reveals several keydifferences in the framework regions of the camelid V_(HH) domaincorresponding to the V_(H)/V_(L) interface of the human V_(H) domains.Mutation of these human residues to V_(HH) resembling residues has beenperformed to produce “camelized” human V_(H) domains that retain antigenbinding activity, yet have improved expression and solubility.

Libraries of single V_(H) domains have also been derived for examplefrom V_(H) genes amplified from genomic DNA or from mRNA from thespleens of immunized mice and expressed in E. coli (Ward et al. (1989)Nature 341: 544-546) and similar approaches can be performed using theV_(H) domains and/or the V_(L) domains described herein. The isolatedsingle VH domains are called “dAbs” or domain antibodies. A “dAb” is anantibody single variable domain (V_(H) or V_(L)) polypeptide thatspecifically binds antigen. A “dAb” binds antigen independently of otherV domains; however, as the term is used herein, a “dAb” can be presentin a homo- or heteromultimer with other V_(H) or V_(L) domains where theother domains are not required for antigen binding by the dAb, i.e.,where the dAb binds antigen independently of the additional V_(H) orV_(L) domains.

As described in U.S. Patent Publication US 2006/0211088 methods areknown for the cloning and direct screening of immunoglobulin sequences(including but not limited to multivalent polypeptides comprising: twoor more variable domains—or antigen binding domains—and in particularV_(H) domains or V_(HH) domains; fragments of V_(L), V_(H) or V_(HH)domains, such as CDR regions, for example CDR3 regions; antigen-bindingfragments of conventional 4-chain antibodies such as Fab fragments andscFv's, heavy chain antibodies and domain antibodies; and in particularof V_(H) sequences, and more in particular of V_(HH) sequences) that canbe used as part of and/or to construct such nanobodies.

Methods and procedures for the production of VHH/nanobodies can also befound for example in WO 94/04678, WO 96/34103, WO 97/49805, WO 97/49805WO 94/25591, WO 00/43507 WO 01/90190, WO 03/025020, WO 04/062551, WO04/041863, WO 04/041865, WO 04/041862, WO 04/041867, PCT/BE2004/000159,Hamers-Casterman et al. (1993) Nature 363: 446; Riechmann andMuyldermans (1999) J. Immunological Meth., 231: 25-38; Vu et al. (1997)Molecular Immunology, 34(16-17): 1121-1131; Nguyen et al. (2000) EMBOJ., 19(5): 921-930; Arbabi Ghahroudi et al. (19997) FEBS Letters 414:521-526; van der Linden et al. (2000) J. Immunological Meth., 240:185-195; Muyldermans (2001) Rev. Molecular Biotechnology 74: 277-302;Nguyen et al. (2001) Adv. Immunol. 79: 261, and the like.

In certain embodiments the antibody targeting moiety is a unibody.Unibodies provide an antibody technology that produces a stable, smallerantibody format with an anticipated longer therapeutic window thancertain small antibody formats. In certain embodiments unibodies areproduced from IgG4 antibodies by eliminating the hinge region of theantibody. Unlike the full size IgG4 antibody, the half molecule fragmentis very stable and is termed a uniBody. Halving the IgG4 molecule leftonly one area on the UniBody that can bind to a target. Methods ofproducing unibodies are described in detail in PCT PublicationWO2007/059782, which is incorporated herein by reference in its entirety(see, also, Kolfschoten et al. (2007) Science 317: 1554-1557).

Affibody molecules are class of affinity proteins based on a 58-aminoacid residue protein domain, derived from one of the IgG-binding domainsof staphylococcal protein A. This three helix bundle domain has beenused as a scaffold for the construction of combinatorial phagemidlibraries, from which Affibody variants that target the desiredmolecules can be selected using phage display technology (see, e.g.,Nord et al. (1997) Nat. Biotechnol. 15: 772-777; Ronmark et al. (2002)Eur. J. Biochem., 269: 2647-2655.). Details of Affibodies and methods ofproduction are known to those of skill (see, e.g., U.S. Pat. No.5,831,012 which is incorporated herein by reference in its entirety).

It will also be recognized that antibodies can be prepared by any of anumber of commercial services (e.g., Berkeley antibody laboratories,Bethyl Laboratories, Anawa, Eurogenetec, etc.).

Illustrative antibodies that bind various microorganisms are shown inTable 11.

TABLE 11 Illustrative antibodies that bind target microorganisms. SourceAntibody U.S. Pat. No. 7,195,763 Polyclonal/monoclonal binds specificGram(+) cell wall repeats U.S. Pat. No. 6,939,543 Antibodies againstG(+) LTA U.S. Pat. No. 7,169,903 Antibodies against G(+) peptidoglycanU.S. Pat. No. 6,231,857 Antibody against S. mutans (Shi) U.S. Pat. No.5,484,591 Gram(−) binding antibodies US 2007/0231321 Diabody binding toStreptococcus surface antigen I/II US 2003/0124635 Antibody against S.mutans US 2006/0127372 Antibodies to Actinomyces naeslundii,Lactobacillus casei US 2003/0092086 Antibody to S. sobrinus U.S. Pat.No. 7,364,738 Monoclonal antibodies to the ClfA protein in S. aureusU.S. Pat. No. 7,632,502 Antibodies against C. albicans U.S. Pat. No.7,608,265 Monoclonal against C. difficile U.S. Pat. No. 4,777,136Monoclonal Antibodies against Pseudomonas aeruginosa see, e.g., ab20429,ab20560, Antibody against S. pneumoniae ab79522, ab35165, ab65602 fromAbCAMm Cambridge Science Park, U.K.

In addition, antibodies (targeting moieties) that bind othermicroorganisms can readily be produced using, for example, the methodsdescribed above.

iii. Porphyrins.

In certain embodiments porphyrins, or other photosensitizing agents, canbe used as targeting moieties in the constructs described herein. Inparticular, metalloporphyrins, particularly a number of non-ironmetalloporphyrins mimic heme in their molecular structure and areactively accumulated by bacteria via high affinity heme-uptake systems.The same uptake systems can be used to deliver antibiotic-porphyrin andantibacterial-porphyrin conjugates. Illustrative targeting porphyrinssuitable for this purpose are described in U.S. Pat. No. 6,066,628 andshown herein, for example, in FIGS. 1 and 2.

For example, certain artificial (non-iron) metalloporphyrins (MPs)(Ga—IX, Mn—IX,) are active against Gram-negative and Gram-positivebacteria and acid-fast bacilli (e.g., Y. enterocolitica, N.meningitides, S. marcescens, E. coli, P. mirabills, K. pneumoniae, K.oxytoca, Ps. aeruginosa, C. freundii, E. aerogenes, F. menigosepticum,S. aureus, B. subtilis, S. pyogenes A, E. faecalis, M. smegmatis, M.bovis, M. tuber., S. crevisiae) as described in Tables 1-5 of U.S. Pat.No. 6,066,628. These MPs can be used as targeting moieties against thesemicroorganisms.

Similarly, some MPs are also growth-inhibitory against yeasts,indicating their usefulness targeting moieties to target Candida species(e.g., Candida albicans, C. krusei, C. pillosus, C. glabrata, etc.) andother mycoses including but not limited to those caused by asTrichophyton, Epidermophyton, Histoplasma, Aspergillus, Cryptococcus,and the like.

Porphyrins, and other photosensitizers, also have antimicrobialactivity. Accordingly, in certain embodiments, the porphyrins, or otherphotosensitizers, can be used as effectors (e.g., attached to targetingpeptides as described herein). In various embodiments the porphyrins orother photosensitizers can provide a dual functionality, e.g., as atargeting moiety and an antimicrobial and can be attached to a targetingpeptide and/or to an antimicrobial peptide as described herein.

Illustrative porphyrins and other photosensitizers are shown in FIGS.1-11 and described in more detail in the discussion of effectors below.

iv. Pheromones.

In certain embodiments, pheromones from microorganisms can be used astargeting moieties. Illustrative pheromones from bacteria and fungi areshown in Table 12.

TABLE 12 Illustrative bacterial and fungal pheromones utilizable astargeting moieties. Locus tag Product Sequence SEQ ID BacterialPheromones gi|1041118|dbj|BAA11198.1| iPD1 [Enterococcus MKQQKKHIAALLF1742 faecalis] ALILTLVS gi|1113947|gb|AAB35253.1| iAM373sex pheromoneSIFTLVA 1743 inhibito [Enterococcus faecalis, Peptide, 7 aa]gi|115412|sp|P13268.1|CAD1_ENTFA Sex pheromone CAD1 LFSLVLAG 1744gi|116406|sp|P11932.1|CIA_ENTFA Sex pheromone cAM373 AIFILAS 1745(Clumping-inducing agent) (CIA) gi|117240|sp|P13269.1|CPD1_ENTFA Sexpheromone cPD1 FLVMFLSG 1746 gi|12056953|gb|AAG48144.1|AF322594_1putative peptide DSIRDVSPTFNKIRR 1747 pheromone PrcA WFDGLFK[Lactobacillus paracasei] gi|123988|sp|P24803.1|IAD1_ENTFA Sex pheromoneinhibitor MSKRAMKKIIPLIT 1748 determinant precursor LFVVTLVG (iAD1)gi|126362994|emb|CAM35812.1| precursor of pheromone KDEIYWKPS 1749peptide ComX [Bacillus amyloliquefaciens FZB42] gi|1587088|prf||2205353Apheromone YSTCDFIM 1750 gi|15900442|ref|NP_345046.1| peptide pheromoneBlpC GLWEDLLYNINRY 1751 [Streptococcus AHYIT pneumoniae TIGR4]gi|1617436|emb|CAA66791.1| competence pheromone DIRHRINNSIWRDIF 1752[Streptococcus gordonii] LKRK gi|1617440|emb|CAA66786.1| competencepheromone DVRSNKIRLWWEN 1753 [Streptococcus gordonii] IFFNKKgi|18307870|gb|AAL67728.1|AF456134_2 ComX pheromone PTTREWDG 1754precursor [Bacillus mojavensis] gi|18307874|gb|AAL67731.1|AF456135_2ComX pheromone LQIYTNGNWVPS 1755 precursor [Bacillus mojavensis]gi|29377808|ref|NP_816936.1| sex pheromone inhibitor MSKRAMKKIIPLIT 1756determinant [Enterococcus LFVVTLVG faecalis V583]gi|3342125|gb|AAC27522.1| putative pheromone GAGKNLIYGMGYG 1757[Enterococcus faecium] YLRSCNRL gi|41018893|sp|P60242.1|CSP1_STRPNCompetence-stimulating EMRLSKFFRDFILQ 1758 peptide type 1 precursor RKK(CSP-1) gi|57489126|gb|AAW51333.1| PcfP [Enterococcus WSEIEINTKQSN 1759faecalis] gi|57489152|gb|AAW51349.1| PrgT [Enterococcus HISKERFEAY 1760faecalis] gi|58616083|ref|YP_195761.1| UvaF [Enterococcus KYKCSWCKRVYTL1761 faecalis] RKDHRTAR gi|58616111|ref|YP_195802.1| PcfP [EnterococcusWSEIEINTKQSN 1762 faecalis] gi|58616132|ref|YP_195769.1| PrgQ[Enterococcus MKTTLKKLSRYIA 1763 faecalis] VVIAITLIFIgi|58616137|ref|YP_195772.1| PrgT [Enterococcus HISKERFEAY 1764faecalis] gi|6919848|sp|O33689.1|CSP_STROR Competence-stimulatingDKRLPYFFKHLFSN 1765 peptide precursor (CSP) RTKgi|6919849|sp|O33666.1|CSP2_STRMT Competence-stimulating EMRKPDGALFNLF1766 peptide precursor (CSP) RRR gi|6919850|sp|O33668.1|CSP3_STRMTCompetence-stimulating EMRKSNNNFFHFL 1767 peptide precursor (CSP) RRIgi|6919851|sp|O33672.1|CSP1_STRMT Competence-stimulating ESRLPKIRFDFIFPR1768 peptide precursor (CSP) KK gi|6919852|sp|O33675.1|CSP4_STRMTCompetence-stimulating EIRQTHNIFFNFFKRR 1769 peptide precursor (CSP)gi|6919853|sp|O33690.1|CSP2_STROR Competence-stimulating DWRISETIRNLIFPR1770 peptide precursor (CSP) RK gi|999344|gb|AAB34501.1| cOB1bacterialsex VAVLVLGA 1771 pheromone [Enterococcus faecalis, Peptide, 8 aa]gi|18307878|gb|AAL67734.1|AF456136_2 ComX pheromone FFEDDKRKSFI 1772precursor [Bacillus subtilis] gi|18307882|gb|AAL67737.1|AF456137_2 ComXpheromone FFEDDKRKSFI 1773 precursor [Bacillus subtilis]gi|28272731|emb|CAD65660.1| accessory gene regulator MKQKMYEAIAHLF 1774protein D, peptide KYVGAKQLVMCC pheromone precursor VGIWFETKIPDELRK[Lactobacillus plantarum WCFS1] gi|28379890|ref|NP_786782.1| accessorygene regulator MKQKMYEAIAHLF 1775 protein D, peptide KYVGAKQLVMCCpheromone precursor VGIWFETKIPDELRK [Lactobacillus plantarum WCFS1]gi|57489105|gb|AAW51312.1| PrgF [Enterococcus VVAYVITQVGAIRF 1776faecalis] gi|58616090|ref|YP_195779.1| PrgF [Enterococcus VVAYVITQVGAIRF1777 faecalis] gi|58616138|ref|YP_195762.1| PrgN [EnterococcusLLKLQDDYLLHLE 1778 faecalis] RHRRTKKIIDEN gi|57489117|gb|AAW51324.1|PcfF [Enterococcus EDIKDLTDKVQSLN 1779 faecalis] ALVQSELNKLIKRK DQSgi|57489119|gb|AAW51326.1| PcfH [Enterococcus WFLDFSDWLSKVP 1780faecalis] SKLWAE gi|58616102|ref|YP_195792.1| PcfF [EnterococcusEDIKDLTDKVQSLN 1781 faecalis] ALVQSELNKLIKRK DQSgi|58616104|ref|YP_195794.1| PcfH [Enterococcus WFLDFSDWLSKVP 1782faecalis] SKLWAE Fungi gi|1127585|gb|AAA99765.1| mfa1 gene productMLSIFAQTTQTSAS 1783 EPQQSPTAPQGRDN GSPIGYSSCVVAgi|1127592|gb|AAA99771.1| mfa2 gene product MLSIFETVAAAAPV 1784TVAETQQASNNEN RGQPGYYCLIA gi|11907715|gb|AAG41298.1| pheromone precursorPSLPSSPPSLLPPLPL 1785 MFalpha1D LKLLATRRPTLVG [Cryptococcus neoformansMTLCV var. neoformans] gi|13810235|emb|CAC37424.1| M-factor precursorMfm1 MDSMANSVSSSSV 1786 [Schizosaccharomyces VNAGNKPAETLNK pombe]TVKNYTPKVPYMC VIA gi|14269436|gb|AAK58071.1|AF378295_1 peptide matingpheromone MDTFTYVDLAAVA 1787 precursor Bbp2-3 AAAVADEVPRDFE[Schizophyllum DQITDYQSYCIIC commune]gi|14269440|gb|AAK58073.1|AF378297_1 peptide mating pheromone SNVHGWCVVA1788 precursor Bbp2-1 [Schizophyllum commune] gi|1813600|gb|AAB41859.1|pheromone precursor NTTAHGWCVVA 1789 Bbp1(1) [Schizophyllum commune]gi|24940428|emb|CAD56313.1| a-pheromone MQPSTVTAAPKDK 1790[Saccharomyces TSAEKKDNYIIKGV paradoxus] FWDPACVIAgi|27549492|gb|AAO17258.1| pheromone phb3.1 GPTWWCVNA 1791 [Coprinopsiscinerea] gi|27549494|gb|AAO17259.1| pheromone phb3.2 SGPTWFCIIQ 1792[Coprinopsis cinerea] gi|27752314|gb|AAO19469.1| pheromone protein aFTAIFSTLSSSVASK 1793 pecursor [Cryptococcus TDAPRNEEAYSSG neoformansvar. grubii] NSP gi|2865510|gb|AAC02682.1| MAT-1 pheromoneMFSIFAQPAQTSVS 1794 [Ustilago hordei] ETQESPANHGANP GKSGSGLGYSTCV VAgi|3023372|sp|P78742.1|BB11_SCHCO RecName: Full = Mating- NTTAHGWCVVA1795 type pheromone BBP1(1); Flags: Precursorgi|3025079|sp|P56508.1|SNA2_YEAST RecName: Full = Protein SDDNYGSLA 1796SNA2 gi|37626077|gb|AAQ96360.1| pheromone precursor Phb3 NGLTFWCVIA 1797B5 [Coprinopsis cinerea] gi|37626081|gb|AAQ96362.1| pheromone precursorPSWFCVIA 1798 Phb3.2 B45 [Coprinopsis cinerea]gi|37626083|gb|AAQ96363.1| pheromone precursor ASWFCTIA 1799 Phb3.1 B47[Coprinopsis cinerea] gi|37961432|gb|AAP57503.1| Ste3-like pheromonePHHKIANASDKRR 1800 receptor [Thanatephorus RMYFEIFMCAVL cucumeris]gi|400250|sp|P31962.1|MFA1_USTMA RecName: Full = A1- MLSIFAQTTQTSAS 1801specific pheromone; EPQQSPTAPQGRDN AltName: Full = Mating GSPIGYSSCVVAfactor A1 gi|400251|sp|P31963.1|MFA2_USTMA RecName: Full = A2-MLSIFETVAAAAPV 1802 specific pheromone; TVAETQQASNNEN AltName: Full= Mating RGQPGYYCLIA factor A2 gi|41209131|gb|AAR99617.1| lipopeptidemating SLTYAWCVVA 1803 pheromone precursor Bap2(3) [Schizophyllumcommune] gi|41209146|gb|AAR99650.1| lipopeptide mating TSMAHAWCVVA 1804pheromone precursor Bap3(2) [Schizophyllum commune]gi|41209149|gb|AAR99653.1| lipopeptide mating GYCVVA 1805 pheromoneprecursor Bbp2(8) [Schizophyllum commune] gi|46098187|gb|EAK83420.1|MFA1_USTMA A1- MLSIFAQTTQTSAS 1806 SPECIFIC PHEROMONE EPQQSPTAPQGRDN(MATING FACTOR A1) GSPIGYSSCVVA [Ustilago maydis 521]gi|546861|gb|AAB30833.1| M-factor mating MDSMANTVSSSVV 1807 pheromoneNTGNKPSETLNKT [Schizosaccharomyces VKNYTPKVPYMCV pombe] IAgi|5917793|gb|AAD56043.1|AF184069_1 pheromone Mfa2 MFSLFETVAAAVK 1808[Ustilago hordei] VVSAAEPEHAPTNE GKGEPAPYCIIAgi|6014618|gb|AAF01424.1|AF186389_1 Phb3.2.42 [Coprinus LTWFCVIA 1809cinereus] gi|68266363|gb|AAY88882.1| putative pheromone LREKRRRRWFEAF1810 receptor STE3.4 MGFGL [Coprinellus disseminatus]gi|71012805|ref|XP_758529.1| A1-specific pheromone MLSIFAQTTQTSAS 1811[Ustilago maydis 521] EPQQSPTAPQGRDN GSPIGYSSCVVAgi|72414834|emb|CAI59748.1| mating factor a1.3 MDALTLFAPVSLG 1812[Sporisorium reilianum] AVATEQAPVDEER PNRQTFPWIGCVVAgi|72414854|emb|CAI59758.1| mating factor a2.1 MFIFESVVASVQAV 1813[Sporisorium reilianum] SVAEQDQTPVSEG RGKPAVYCTIAgi|1127587|gb|AAA99767.1| rba1 gene product PWMSLLFSFLALLA 1814LILPKLSKDDPLGL TRQPR gi|151941959|gb|EDN60315.1| pheromone-regulatedASISLIMEGSANIEA 1815 membrane protein VGKLVWLAAALPL [Saccharomycescerevisiae AFI YJM789] gi|3025095|sp|Q07549.1|SNA4_YEAST Protein SNA4ARNVYPSVETPLLQ 1816 GAAPHDNKQSLVE SPPPYVPgi|73921293|sp|Q08245.3|ZEO1_YEAST RecName: Full = ProteinFLKKLNRKIASIFN 1817 ZEO1; AltName: Full = Zeocin resistance protein 1gi|74644573|sp|Q9P305.3|IGO2_YEAST RecName: Full = ProteinDSISRQGSISSGPPP 1818 EDF (E. coli) IGO2 RSPNK NNWNN 1819

v. Targeting Enhancers/Opsonins

In certain embodiments compositions are contemplated that incorporate atargeting enhancer (e.g., an opsonin) along with one or more targetingmoieties (e.g., targeting peptides). Targeting enhancers includemoieties that increase binding affinity, and/or binding specificity,and/or internalization of a moiety by the target cell/microorganism.

Accordingly, in certain embodiments, a targeting moiety and/or atargeted antimicrobial molecule comprise a peptide, with the desiredlevel of binding specificity and/or avidity, attached (e.g., conjugated)to an opsonin. When bound to a target cell through the targetingpeptide, the opsonin component encourages phagocytosis and destructionby resident macrophages, dendritic cells, monocytes, or PMNs. Opsoninscontemplated for conjugation can be of a direct or indirect type.

Direct opsonins include, fore example, any bacterial surface antigen,PAMP (pathogen-associated molecular pattern), or other moleculerecognized by host PRRs (pathogen recognizing receptors). Opsonins caninclude, but are not limited to, bacterial protein, lipid, nucleic acid,charbohydrate and/or oligosaccharide moieties.

In certain embodiments opsonins include, but are not limited to,N-acetyl-D-glucosamine (GlcNAc), N-acetyl-D-galactosamine (GlaNAc),N-acetylglucosamine-containing muramyl peptides, NAG-muramyl peptides,NAG-NAM, peptidoglycan, teichoic acid, lipoteichoic acid, LPS,o-antigen, mannose, fucose, ManNAc, galactose, maltose, glucose,glucosamine, sucrose, mannosamine,galactose-alpha-1,3-galactosyl-beta-1,4-N-acetyl glucosamine, oralpha-1,3-gal-gal, or other sugars.

In certain embodiments, opsonins include indirect opsonins Indirectopsonins function through binding to a direct opsonin already present.For example an Fc portion of an antibody, a sugar-binding lectin protein(example MBL), or host complement factors (example C3b, C4b, iC3b).

In certain embodiments the opsonin is togalactose-alpha-1,3-galactosyl-beta-1,4-N-acetyl glucosamine, oralpha-1,3-gal-gal.

Other examples of opsonin molecules include, but are not limited toantibodies (e.g., IgG and IgA), components of the complement system(e.g., C3b, C4b, and iC3b), mannose-binding lectin (MBL) (initiates theformation of C3b), and the like.

Methods of coupling an opsonin to a targeting moiety are well known tothose of skill in the art (see, e.g., discussion below regardingattachment of effectors to targeting moieties).

B) Effectors.

Any of a wide number of effectors can be coupled to targeting moietiesas described herein to preferentially deliver the effector to a targetorganism and/or tissue. Illustrative effectors include, but are notlimited to detectable labels, small molecule antibiotics, antimicrobialpeptides, porphyrins or other photosensitizers, epitope tags/antibodiesfor use in a pretargeting protocol, agents that physically disrupt theextracellular matrix within a community of microorganisms,microparticles and/or microcapsules, nanoparticles and/or nanocapsules,“carrier” vehicles including, but not limited to lipids, liposomes,dendrimers, cholic acid-based peptide mimics or other peptide mimics,steroid antibiotics, and the like.

i. Detectable Labels.

In certain embodiments chimeric moieties are provided comprising atargeting moiety (e.g., as described in Table 3) attached directly orthrough a linker to a detectable label. Such chimeric moieties areeffective for detecting the presence and/or quantity, and/or location ofthe microorganism(s) to which the targeting moiety is directed.Similarly these chimeric moieties are useful to identify cells and/ortissues and/or food stuffs and/or other compositions that are infectedwith the targeted microorganism(s).

Detectable labels suitable for use in such chimeric moieties include anycomposition detectable by spectroscopic, photochemical, biochemical,immunochemical, electrical, optical, or chemical means. Illustrativeuseful labels include, but are not limited to, biotin for staining withlabeled streptavidin conjugates, avidin or streptavidin for labelingwith biotin conjugates fluorescent dyes (e.g., fluorescein, texas red,rhodamine, green fluorescent protein, and the like, see, e.g., MolecularProbes, Eugene, Oreg., USA), radiolabels (e.g., ³H, ¹²⁵I, ³⁵S, ¹⁴C, ³²P,⁹⁹Tc, ²⁰³Pb, ⁶⁷Ga, ⁶⁸Ga, ⁷²As, ¹¹¹In, ^(113m)In, ⁹⁷Ru, ⁶²Cu, 641Cu,⁵²Fe, ^(52m)Mn, ⁵¹Cr, ¹⁸⁶Re, ¹⁸⁸Re, ⁷⁷As, ⁹⁰Y, ⁶⁷Cu, ¹⁶⁹Er, ¹²¹Sn,¹²⁷Te, ¹⁴²Pr, ¹⁴³Pr, ¹⁹⁸Au, ¹⁹⁹Au, ¹⁶¹Tb, ¹⁰⁹Pd, ¹⁶⁵Dy, ¹⁴⁹Pm, ¹⁵¹Pm,¹⁵³Sm, ¹⁵⁷Gd, ¹⁵⁹Gd, ¹⁶⁶Ho, ¹⁷²Tm, ¹⁶⁹Yb, ¹⁷⁵Yb, ¹⁷⁷Lu, ¹⁰⁵Rh, ¹¹¹Ag,and the like), enzymes (e.g., horse radish peroxidase, alkalinephosphatase and others commonly used in an ELISA), various colorimetriclabels, magnetic or paramagnetic labels (e.g., magnetic and/orparamagnetic nanoparticles), spin labels, radio-opaque labels, and thelike. Patents teaching the use of such labels include, for example, U.S.Pat. Nos. 3,817,837; 3,850,752; 3,939,350; 3,996,345; 4,277,437;4,275,149; and 4,366,241.

It will be recognized that fluorescent labels are not to be limited tosingle species organic molecules, but include inorganic molecules,multi-molecular mixtures of organic and/or inorganic molecules,crystals, heteropolymers, and the like. Thus, for example, CdSe-CdScore-shell nanocrystals enclosed in a silica shell can be easilyderivatized for coupling to a biological molecule (Bruchez et al. (1998)Science, 281: 2013-2016). Similarly, highly fluorescent quantum dots(zinc sulfide-capped cadmium selenide) have been covalently coupled tobiomolecules for use in ultrasensitive biological detection (Warren andNie (1998) Science, 281: 2016-2018).

In various embodiments spin labels are provided by reporter moleculeswith an unpaired electron spin which can be detected by electron spinresonance (ESR) spectroscopy. Illustrative spin labels include organicfree radicals, transitional metal complexes, particularly vanadium,copper, iron, and manganese, and the like. Exemplary spin labelsinclude, for example, nitroxide free radicals.

Means of detecting such labels are well known to those of skill in theart. Thus, for example, where the label is a radioactive label, meansfor detection include a scintillation counter or photographic film as inautoradiography. Where the label is a fluorescent label, it may bedetected by exciting the fluorochrome with the appropriate wavelength oflight and detecting the resulting fluorescence, e.g., by microscopy,visual inspection, via photographic film, by the use of electronicdetectors such as charge coupled devices (CCDs) or photomultipliers andthe like. Similarly, enzymatic labels may be detected by providingappropriate substrates for the enzyme and detecting the resultingreaction product. Finally, simple colorimetric labels may be detectedsimply by observing the color associated with the label.

ii. Antibiotics.

In certain embodiments chimeric moieties are provided comprising atargeting moiety (e.g. as described in Table 3) attached directly orthrough a linker to a small molecule antibiotic and/or to a carrier(e.g., a lipid or liposome, a polymer, etc.) comprising a small moleculeantibiotic. Illustrative antibiotics are shown in Table 13.

TABLE 13 Illustrative antibiotics for use in the chimeric moietiesdescribed herein. Class Generic Name BRAND NAME Aminoglycosides AmikacinAMIKIN ® Gentamicin GARAMYCIN ® Kanamycin KANTREX ® Neomycin NetilmicinNETROMYCIN ® Streptomycin Tobramycin NEBCIN ® Paromomycin HUMATIN ®Carbacephem Loracarbef LORABID ® Carbapenems Ertapenem INVANZ ®Doripenem FINIBAX ® Imipenem/Cilastatin PRIMAXIN ® Meropenem MERREM ®Cephalosporins Cefadroxil DURICEF ® (First generation) Cefazolin ANCEF ®Cefalotin or Cefalothin KEFLIN ® Cefalexin KEFLEX ® CephalosporinsCefaclor CECLOR ® (Second Cefamandole MANDOLE ® generation) CefoxitinMEFOXIN ® Cefprozil CEFZIL ® Cefuroxime CEFTIN, ZINNAT ® CephalosporinsCefixime SUPRAX ® (Third Cefdinir OMNICEF ® generation) CefditorenSPECTRACEF ® Cefoperazone CEFOBID ® Cefotaxime CLAFORAN ® CefpodoximeCeftazidime FORTAZ ® Ceftibuten CEDAX ® Ceftizoxime CeftriaxoneROCEPHIN ® Cephalosporins Cefepime MAXIPIME ® (Fourth generation)Cephalosporins Ceftobiprole (Fifth generation) Glycopeptides TeicoplaninVancomycin VANCOCIN ® Macrolides Azithromycin Zithromax ClarithromycinBiaxin Dirithromycin Erythromycin Erythocin, Erythroped RoxithromycinTroleandomycin Telithromycin Ketek Monobactams Aztreonam PenicillinsAmoxicillin NOVAMOX ®, AMOXIL ® Ampicillin Azlocillin CarbenicillinCloxacillin Dicloxacillin Flucloxacillin FLOXAPEN ® MezlocillinMeticillin Nafcillin Oxacillin Penicillin Piperacillin TicarcillinPolypeptides Bacitracin Colistin Polymyxin B Quinolones MafenideProntosil (archaic) Sulfacetamide Sulfamethizole Sulfanilimide (archaic)Sulfasalazine Sulfisoxazole Trimethoprim BACTRIM ® Trimethoprim-Sulfamethoxazole (Co- trimoxazole) (TMP-SMX) TetracyclinesDemeclocycline Doxycycline VIBRAMYCIN ® Minocycline MINOCIN ®Oxytetracycline TERRACIN ® Tetracycline SUMYCIN ® Natural productsAntimicrobial herbal extracts Essential oils Farnesol Licorice rootextracts Glycyrrhizol A Glycyrrhizol B 6,8-diisoprenyl-5,7,4′-trihydroxyisoflavone Others Arsphenamine SALVARSAN ® ChloramphenicolCHLOROMYCETIN ® Clindamycin CLEOCIN ® Lincomycin Ethambutol FosfomycinFusidic acid FUCIDIN ® Furazolidone Isoniazid Linezolid ZYVOX ®Metronidazole FLAGYL ® Mupirocin BACTROBAN ® NitrofurantoinMACRODANTIN ®, MACROBID ® Platensimycin PyrazinamideQuinupristin/Dalfopristin SYNCERCID ® Rifampin or Rifampicin TinidazoleArtemisinin Antifungals Amphotericin B Anidulafungin Caspofungin acetateClotrimazole Fluconazole Flucytosine Griseofulvin ItraconazoleKetoconazole Micafungin Miconazole Nystatin Pentamidine PosaconazoleTerbinafine Voriconazole Antimycobiotics Aminosalicylic Acid CapreomycinClofazimine Cycloserine Ethionamide Rifabutin Rifapentine AntiviralsAbacavir Acyclovir Adefovir Amantadine Atazanavir Cidofovir DarunavirDidanosine Docosanol Efavirenz Emtricitabine Enfuvirtide EntecavirEtravirine Famciclovir Fomivirsen Fosamprenavir Foscarnet GanciclovirIdoxuridine Indinavir Interferon alpha Lamivudine Lopinavir/ritonavirMaraviroc Nelfinavir Nevirapine Oseltamivir Penciclovir PeramivirRaltegravir Ribavirin Rimantadine Ritonavir Saquinavir StavudineTelbivudine Tenofovir Tipranavir Trifluridine ValacyclovirValganciclovir Zanamivir Zidovudine Anti-parasitics AlbendazoleArtesunate Atovaquone Bephenium hydroxynaphthoate Chloroquine DapsoneDiethyl-carbamazine Diloxanide furoate Eflornithine Emetine HClFurazolidone Ivermectin Lindane Mebendazole Mefloquine MelarsoprolMiltefosine Niclosamide Nifurtimox Nitazoxanide Oxamniquine ParomomycinPermethrin Piperazine Praziquantel Primaquine Pyrantel pamoatePyrimethamine Proguanil Quinacrine HCl Quinidine Quinine SodiumStibogluconate Spiramycin Thiabendazole Tinidazole

iii. Porphyrins and Non-Porphyrin Photosensitizers.

In certain embodiments, porphyrins and other photosensitizers can beused as targeting moieties and/or as effectors in the methods andcompositions of this invention. A photosensitizer is a drug or otherchemical that increases photosensitivity of the organism (e.g.,bacterium, yeast, fungus, etc.). As targeting moieties thephotosensitizers (e.g., porphyrins) are preferentially uptaken by thetarget microorganisms and thereby facilitate delivery of the chimericmoiety to the target microorganism.

As effectors, photosensitizers can be useful in photodynamicantimicrobial chemotherapy (PACT). In various embodiments PACT utilizesphotosensitizers and light (e.g., visible, ultraviolet, infrared, etc.)in order to give a phototoxic response in the target organism(s), oftenvia oxidative damage.

Currently, the major use of PACT is in the disinfection of bloodproducts, particularly for viral inactivation, although moreclinically-based protocols are used, e.g. in the treatment of oralinfection or topical infection. The technique has been shown to beeffective in vitro against bacteria (including drug-resistant strains),yeasts, viruses, parasites, and the like.

Attaching a targeting moiety (e.g., a targeting peptide) to thephotosensitizer, e.g., as described herein, provides a means ofspecifically or preferentially targeting the photosensitizer(s) toparticular species or strains(s) of microorganism.

A wide range of photosensitizers, both natural and synthetic are knownto those of skill in the art (see, e.g., Wainwright (1998) J.Antimicrob. Chemotherap. 42: 13-28). Photosensitizers are available withdiffering physicochemical make-up and light-absorption properties. Invarious embodiments photosensitizers are usually aromatic molecules thatare efficient in the formation of long-lived triplet excited states. Interms of the energy absorbed by the aromatic-system, this again dependson the molecular structure involved. For example: furocoumarinphotosensitizers (psoralens) absorb relatively high energy ultraviolet(UV) light (c. 300-350 nm), whereas macrocyclic, heteroaromaticmolecules such as the phthalocyanines absorb lower energy, near-infraredlight.

Illustrative photosensitizers include, but are not limited toporphyrinic macrocyles (especially porphyrins, chlorines, etc., see,e.g., FIGS. 1 and 2). In particular, metalloporphyrins, particularly anumber of non-iron metalloporphyrins mimic haem in their molecularstructure and are actively accumulated by bacteria via high affinityhaem-uptake systems. The same uptake systems can be used to deliverantibiotic-porphyrin and antibacterial-porphyrin conjugates.Illustrative targeting porphyrins suitable for this purpose aredescribed in U.S. Pat. No. 6,066,628 and shown herein in FIGS. 1 and 2.

Illustrative examples of targeted porphyrins are described in Example 5and associated figures and in FIG. 13.

For example, certain artificial (non-iron) metalloporphyrins (MPs)(Ga—IX, Mn—IX,) are active against Gram-negative and Gram-positivebacteria and acid-fast bacilli (e.g., Y. enterocolitica, N.meningitides, S. marcescens, E. coli, P. mirabills, K. pneumoniae, K.oxytoca, Ps. aeruginosa, C. freundii, E. aerogenes, F. menigosepticum,S. aureus, B. subtilis, S. pyogenes A, E. faecalis, M. smegmatis, M.bovis, M tuber., S. crevisiae) as described in Tables 1-5 of U.S. Pat.No. 6,066,628. These MPs can be used as targeting moieties against thesemicroorganisms.

Similarly, some MPs are also growth-inhibitory against yeasts,indicating their usefulness targeting moieties to target Candida species(e.g., Candida albicans, C. krusei, C. pillosus, C. glabrata, etc.) andother mycoses including but not limited to those caused by asTrichophyton, Epidermophyton, Histoplasma, Aspergillus, Cryptococcus,and the like.

Other photosensitizers include, but are not limited to cyanines (see,e.g., FIG. 6) and phthalocyanines (see, e.g., FIG. 4), azines (see,e.g., FIG. 5) including especially methylene blue and touidine blue,hypericin (see, e.g., FIG. 8), acridines (see, e.g., FIG. 9) includingespecially Rose Bengal (see, e.g., FIG. 10), crown ethers (see, e.g.,FIG. 11), and the like. In certain embodiments, the photosensitizersinclude tin chlorin 6 and related compounds (e.g., other chlorines andtin porphyrins).

Another light-activated compound is cucumin (see, FIG. 12).

In certain embodiments the photosensitizers are toxic or growthinhibitors without light activation. For example, some non-ironmetalloporphyrins (MPs) (see, e.g., FIGS. 1 and 2 herein) possess apowerful light-independent antimicrobial activity. In addition, haemin,the most well known natural porphyrin, possesses a significantantibacterial activity that can augmented by the presence ofphysiological concentrations of hydrogen peroxide or a reducing agent.

Typically, when activated by light, the toxicity or growth inhibitioneffect is substantially increased. Typically, they generate radicalspecies that affect anything within proximity. In certain embodiments toget the best selectivity from targeted photosensitizers, anti-oxidantscan be used to quench un-bound photosensitizers, limiting the damageonly to cells where the conjugates have accumulated due to the targetingpeptide. The membrane structures of the target cell act as the protondonors in this case.

In typical photodynamic antimicrobial chemotherapy (PACT) the targetedphotosensitizer is “activated by the application of a light source(e.g., a visible light source, an ultraviolate light source, an infraredlight source, etc.). PACT applications however need not be limited totopical use. Regions of the mouth, throat, nose, sinuses are readilyilluminated. Similarly regions of the gut can readily be illuminatedusing endoscopic techniques. Other internal regions can be illuminedusing laparoscopic methods or during other surgical procedures. Forexample, in certain embodiments involving the insertion or repair orreplacement of an implantable device (e.g., a prosthetic device) itcontemplated that the device can be coated or otherwise contacted with achimeric moiety comprising a targeting moiety attached to aphotosensitizer as described herein. During the surgical procedureand/or just before closing, the device can be illuminated with anappropriate light source to activate the photosensitizer.

The targeted photosensitizers and uses thereof described herein areillustrative and not to be limiting. Using the teachings providedherein, other targeted photosensitizers and uses thereof will beavailable to one of skill in the art.

iv. Antimicrobial Peptides.

In certain embodiments, the effector can comprise one or moreantimicrobial peptides or compound antimicrobial peptides, e.g., asdescribed above. Numerous antimicrobial peptides are well known to thoseof skill in the art.

In certain embodiments the antimicrobial peptides comprise one or moreamino acid sequences described above (e.g., one or more domainscomprising amino acid sequences in Tables 4 and/or 5) and/or one or moreof the amino acid sequences shown in Table 14. In certain embodimentsthe antimicrobial peptides comprise one or more amino acid sequencesdescribed in the “Collection of Anti-Microbial Peptides” (CAMP) anonline database developed for advancement the understanding ofantimicrobial peptides (see, e.g., Thomas et al. (2009) Nucleic AcidsResearch, 2009, 1-7.doi:10.1093/nar/gkp1021) available atwww.bicnirrh.res.in/antimicrobial.

TABLE 14 Other illustrative antimicrobial peptides. AP numbers refer toID in antimicrobial peptide database (http://aps.unmc.edu/AP/main.php).SEQ ID Effector Structure/Sequence No AP00274 1BH4, Circulin AGIPCGESCVWIPCISAALGCSCKNK 1820 (CirA, plant VCYRN cyclotides, XXC, ZZHp)AP00036 1BNB, Beta- DFASCHTNGGICLPNRCPGHMIQIG 1821 defensin 1 (cow)ICFRPRVKCCRSW AP00047 1BNB, Bovine GPLSCGRNGGVCIPIRCPVPMRQIG 1822neutrophil beta- TCFGRPVKCCRSW defensin 12 (BNBD-12, cow) AP00428 1C01,MiAMP1 SAFTVWSGPGCNNRAERYSKCGCS 1823 (Macadamia AIHQKGGYDFSYTGQTAALYNQAintegrifolia GCSGVAHTRFGSSARACNPFGWKS antimicrobial IFIQC peptide 1,plant) AP00154 1CIX, Tachystatin YSRCQLQGFNCVVRSYGLPTIPCC 1824 A2(Horseshoe RGLTCRSYFPGSTYGRCQRY crabs, Crustacea, BBS) AP00145 1CW5,VNYGNGVSCSKTKCSVNWGQAFQ 1825 Carnobacteriocin ERYTAGINSFVSGVASGAGSIGRRPB2 (CnbB2, class IIA bacteriocin, bacteria) AP00153 1CZ6, AndroctoninRSVCRQIKICRRRGGCYYKCTNRPY 1826 (scorpions) AP00152 1D6X, TritrpticinVRRFPWWWPFLRR 1827 (synthetic) AP00201 1D7N, Mastoparan INLKALAALAKKIL1828 (insect) AP00140 1D9J, CecropinA- KWKLFKKIGIGKFLHSAKKF 1829Magainin2 hybrid (synthetic) AP00178 1DFN, humanDCYCRIPACIAGERRYGTCIYQGRL 1830 alpha Defensin WAFCC HNP-3 (humanneutrophil peptide- 3, HNP3, human defensin, ZZHh) AP01153 1DQC,Tachycitin YLAFRCGRYSPCLDDGPNVNLYSC 1831 (horseshoe crabs,CSFYNCHKCLARLENCPKGLHYN Crustacea, BBS) AYLKVCDWPSKAGCT AP00437 1DUM,Magainin 2 GIGKYLHSAKKFGKAWVGEIMNS 1832 analog (synthetic) AP00451 1E4S,Human beta DHYNCVSSGGQCLYSACPIFTKIQG 1833 defensin 1 (HBD-1, TCYRGKAKCCKhuman defensin) AP00149 1EWS, Rabbit MPCSCKKYCDPWEVIDGSCGLFNS 1834kidney defensin 1 KYICCREK (RK-1) AP00141 1F0E, CecropinA-KWKLFKKIPKFLHSAKKF 1835 Magainin2 Hybrid (P18, synthetic) AP00142 1F0G,CecropinA- KLKLFKKIGIGKFLHSAKKF 1836 Magainin2 Hybrid (synthetic)AP00143 1F0H, CecropinA- KAKLFKKIGIGKFLHSAKKF 1837 Magainin2 Hybrid(synthetic) AP00524 1FD4, Human beta GIGDPVTCLKSGAICHPVFCPRRYK 1838defensin 2 (HBD-2, QIGTCGLPGTKCCKKP human defensin, ZZHh) AP00438 1FJN,Mussel GFGCPNNYQCHRHCKSIPGRCGGY 1839 Defensin MGD-1 CGGWHRLPCTCYRCGAP00155 1FRY, SMAP-29 RGLRRLGRKIAHGVKKYGPTVLRII 1840 (SMAP29, sheep RIAGcathelicidin) AP00150 1G89, Indolicidin ILPWKWPWWPWRR 1841 (cowcathelicidin, BBN, ZZHa) AP00156 1GR4, Microcin VGIGTPISFYGGGAGHVPEYF1842 J25, linear (MccJ25, bacteriocin, bacteria) AP00151 1HR1,Indolicidin ILAWKWAWWAWRR 1843 P to A mutant (synthetic) AP00196 1HU5,Ovispirin-1 KNLRRIIRKIIHIIKKYG 1844 (synthetic) AP00197 1HU6, NovispirinKNLRRIIRKGIHIIKKYG 1845 G10 (synthetic) AP00198 1HU7, NovispirinKNLRRITRKIIHIIKKYG 1846 T7 (synthetic) AP00445 1HVZ, MonkeyGFCRCLCRRGVCRCICTR 1847 RTD-1 (rhesus theta-defensin-1, minidefensin-1,animal defensin, XXC, BBS, lectin, ZZHa) AP00103 1i2v, HeliomicinDKLIGSCVWGAVNYTSDCNGECL 1848 variant (Hel-LL, LRGYKGGHCGSFANVNCWCETsynthetic) AP00216 1ICA, Phormia ATCDLLSGTGINHSACAAHCLLRG 1849 defensinA (insect NRGGYCNGKGVCVCRN defensin A) AP01224 1Jo3, Gramicidin BVGALAVVVWLFLWLW 1850 (bacteria) AP01225 1jo4, Gramicidin CVGALAVVVWLYLWLW 1851 (bacteria) AP00191 1KFP, Gomesin ECRRLCYKQRCVTYCRGR1852 (Gm, Spider, XXA) AP00283 1KJ6, Huamn beta GIINTLQKYYCRVRGGRCAVLSCL1853 defensin 3 (HBD-3, PKEEQIGKCSTRGRKCCRRKK human defensin, ZZHh)AP00147 1KV4, Moricin AKIPIKAIKTVGKAVGKGLRAINIA 1854 (insect, silk moth)STANDVFNFLKPKKRKA AP00227 1L4V, Sapecin ATCDLLSGTGINHSACAAHCLLRG 1855(insect, flesh fly) NRGGYCNGKAVCVCRN AP01161 1L9L, HumanGRDYRTCLTIVQKLKKMVDKPTQ 1856 granulysin RSVSNAATRVCTRGRSRWRDVCR (huGran)NFMRRYQSRVIQGLVAGETAQQIC EDLRLCIPSTGPL AP00026 1LFC,FKCRRWQWRMKKLGAPSITCVRR 1857 Lactoferricin B AF (LfcinB, cow, ZZHa)AP00193 1M4F, human DTHFPICIFCCGCCHRSKCGMCCKT 1858 LEAP-1 (Hepcidin 25)AP00499 1MAG, Gramicidin VGALAVVVWLWLWLW 1859 A (gA, bacteria) AP004031MM0, Termicin ACNFQSCWATCQAQHSIYFRRAFC 1860 (termite defensin,DRSQCKCVFVRG insect defensin) AP00194 1MMC, Ac-AMP2VGECVRGRCPSGMCCSQFGYCGK 1861 (plant defensin, GPKYCGR BBS) AP01206 1MQZ,Mersacidin CTFTLPGGGGVCTLTSECIC 1862 (bacteria) AP00429 1NKL, PorcineGYFCESCRKIIQKLEDMVGPQPNE 1863 NK-Lysin (pig) DTVTQAASQVCDKLKILRGLCKKIMRSFLRRISWDILTGKKPQAICVDI KICKE AP00633 1og7, Sakacin P/KYYGNGVHCGKHSCTVDWGTAIG 1864 Sakacin 674 (SakP, NIGNNAAANWATGGNAGWNKclass IIA bacteriocin, bacteria) AP00195 1PG1, Protegrin 1RGGRLCYCRRRFCVCVGR 1865 (Protegrin-1, PG-1, pig cathelicidin, XXA, ZZHa,BBBm) AP00928 1PXQ, Subtilosin NKGCATCSIGAACLVDGPIPDFEIA 1866 A (XXC,class I GATGLFGLWG bacteriocin, Gram- positive bacteria) AP00480 1Q71,Microcin VGIGTPIFSYGGGAGHVPEYF 1867 J25 (cyclic MccJ25, class Imicrocins, bacteriocins, Gram- negative bacteria, XXC; BBP) AP002111RKK, RRWCFRVCYRGFCYRKCR 1868 Polyphemusin I (crabs, Crustacea) AP004301T51, IsCT ILGKIWEGIKSLF 1869 (Scorpion) AP00731 1ut3, Spheniscin-2SFGLCRLRRGFCARGRCRFPSIPIGR 1870 (Sphe-2, penguin CSRFVQCCRRVW defensin,avian defensin) AP00013 1VM5, Aurein 1.2 GLFDIIKKIAESF 1871 (frog)AP00214 1WO1, KWCFRVCYRGICYRRCR 1872 Tachyplesin I (crabs, Crustacea,XXA, ZZHa) AP00644 1xc0, Pardaxin 4 GFFALIPKIISSPLFKTLLSAVGSALS 1873(Pardaxin P-4, SSGGQE Pardaxin P4, Pa4, flat fish) AP00493 1XKM,Distinctin NLVSGLIEARKYLEQLHRKLKNCKV 1874 (two chains for stability andtransport? frog) AP00420 1XV3, Penaeidin- HSSGYTRPLRKPSRPIFIRPIGCDVC1875 4d (penaeidin 4, YGIPSSTARLCCFRYGDCCHL shrimp, Crustacea) AP000351YTR, Plantaricin KSSAYSLQMGATAIKQVKKLFKK 1876 A (PlnA, WGW bacteriocin,bacteria) AP00166 1Z64, Pleurocidin GWGSFFKKAAHVGKHVGKAALT 1877 (fish)HYL AP00780 1Z6V, Human GRRRRSVQWCAVSQPEATKCFQW 1878 lactoferricinQRNMRKVRGPPVSCIKRDSPIQCIQA AP00549 1ZFU, PlectasinGFGCNGPWDEDDMQCHNHCKSIK 1879 (fungi, fungal GYKGGYCAKGGFVCKCY defensin)AP00177 1ZMH, human CYCRIPACIAGERRYGTCIYQGRL 1880 alpha Defensin WAFCCHNP-2 (human neutrophil peptide- 2, HNP2, human defensin, ZZHh) AP001791ZMM, human VCSCRLVFCRRTELRVGNCLIGGV 1881 alpha Defensin SFTYCCTRVDHNP-4 (human neutrophil peptide- 4, HNP4, human defensin) AP00180 1ZMP,human QARATCYCRTGRCATRESLSGVCE 1882 alpha Defensin ISGRLYRLCCR HD-5(HD5, human defensin) AP00181 1ZMQ, human STRAFTCHCRRSCYSTEYSYGTCT 1883alpha Defensin VMGINHRFCCL HD-6 (HD6, human defensin) AP00399 1ZRW,Spinigerin HVDKKVADKVLLLKQLRIMRLLT 1884 (insect, termite) RL AP011571ZRX, Stomoxyn RGFRKHFNKLVKKVKHTISETAHV 1885 (insect) AKDTAVIAGSGAAVVAATAP00637 2A2B, Curvacin A/ ARSYGNGVYCNNKKCWVNRGEA 1886 sakacin A (CurA,TQSIIGGMISGWASGLAGM SakA, class IIA bacteriocin, bacteria) AP00558 2B68,Cg-Def GFGCPGNQLKCNNHCKSISCRAGY 1887 (Crassostrea gigasCDAATLWLRCTCTDCNGKK defensin, oyster defensin, animal defensin) AP011542B9K, LCI AIKLVQSPNGNFAASFVLDGTKWI 1888 (bacteria)FKSKYYDSSKGYWVGIYEVWDRK AP01005 2DCV, TachystatinYVSCLFRGARCRVYSGRSCCFGYY 1889 B1 (BBS, CRRDFPGSIFGTCSRRNF horseshoecrabs) AP01006 2DCW, YITCLFRGARCRVYSGRSCCFGYY 1890 Tachystatin B1CRRDFPGSIFGTCSRRNF (BBS, horseshoe crabs) AP00275 2ERI, Circulin BCGESCVFIPCISTLLGCSCKNKVCY 1891 (CirB, plant RNGVIP cyclotides, XXC,ZZHp) AP00707 2f3a, LLAA (LL- RLFDKIRQVIRKF 1892 37-derived aurein 1.2analog, retro- FK13, synthetic) AP00708 2fbs, FK-13 (FK13, FKRIVQRIKDFLR1893 NMR-discovered LL-37 core peptide, XXA, ZZHs, synthetic) AP000882G9L, Gaegurin-4 GILDTLKQFAKGVGKDLVKGAAQ 1894 (Gaegurin 4, frog)GVLSTVSCKLAKTC AP01011 2G9P, Latarcin 2a GLFGKLIKKFGRKAISYAVKKARG 1895(Ltc2a, BBM, KH spider) AP00612 2GDL, Fowlicidin-LVQRGRFGRFLRKIRRFRPKVTITI 1896 2 (chCATH-2, bird QGSARFG cathelicidin,chicken cathelicidin, BBL) AP00402 2GL1, VrD2 KTCENLANTYRGPCFTTGSCDDHC1897 (Vigna radiata KNKEHLRSGRCRDDFRCWCTRNC defensin 2, plant defensin,mung bean) AP00285 2GW9, Cryptdin-4 GLLCYCRKGHCKRGERVRGTCGIR 1898 (Crp4,animal FLYCCPRR defensin, alpha, mouse) AP00613 2hfr, Fowlicidin-3RVKRFWPLVPVAINTVAAGINLYK 1899 (chCATH-3, bird AIRRK cathelicidin,chicken cathelicidin) AP01007 2JMY, CM15 KWKLFKKIGAVLKVL 1900(Synthetic) AP00728 2jni, Arenicin-2 RWCVYAYVRIRGVLVRYRRCW 1901 (marinepolychaeta, BBBm) AP00473 2jos, Piscidin 1 FFHHIFRGIVHVGKTIHRLVTG 1902(fish) AP01151 2JPJ, Lactococcin GTWDDIGQGIGRVAYWVGKALGN 1903 G-a (chaina, class LSDVNQASRINRKKKH IIb bacteriocin, bacteria. For chain b, seeinfo) AP00757 2jpy, Phylloseptin- FLSLIPHAINAVSTLVHHF 1904 H2 (PLS-H2,Phylloseptin-2, PS- 2) (XXA, frog) AP00546 2jq0, Phylloseptin-FLSLIPHAINAVSAIAKHN 1905 1 (Phylloseptin-H1, PLS-H1, PS-1, XXA, frog)AP00758 2jq1, Phylloseptin- FLSLIPHAINAVSALANHG 1906 3 (Phylloseptin-H3,PLS-H3, PS-3) (XXA, frog) AP00727 2jsb, Arenicin-1 RWCVYAYVRVRGVLVRYRRCW1907 (marine polychaeta, BBBm) AP00592 2k10, Ranatuerin-GILSSFKGVAKGVAKDLAGKLLET 1908 2CSa (frog) LKCKITGC AP00485 2K38,Cupiennin GFGALFKFLAKKVAKTVAKQAAK 1909 1a (spider) QGAKYVVNKQME AP003102K6O, Human LL- LLGDFFRKSKEKIGKEFKRIVQRIK 1910 37 (LL37, humanDFLRNLVPRTES cathelicidin; released by proteinase 3 from its precursorin neutrophils; FALL- 39; BBB, BBM, BBP, BBW, BBD, BBL, ZZHh) AP001992LEU, Leucocin A KYYGNGVHCTKSGCSVNWGEAFS 1911 (LeuA, class IIaAGVHRLANGGNGFW bacteriocin, bacteria) AP00144 2MAG, Magainin 2GIGKFLHSAKKFGKAFVGEIMNS 1912 (frog) AP00146 2MLT, MelittinGIGAVLKVLTTGLPALISWIKRKRQQ 1913 (insect, ZZHa) AP01010 2PCO, Latarcin 1SMWSGMWRRKLKKLRNALKKKL 1914 (Ltc1, BBM, KGEK spider) AP00176 2PM1, humanACYCRIPACIAGERRYGTCIYQGRL 1915 alpha Defensin WAFCC HNP-1 (humanneutrophil peptide- 1, HNP1, human defensin, ZZHh) AP01158 2RLG, RP-1ALYKKFKKKLLKSLKRL 1916 (synthetic) AP00102 8TFV, ThanatinGSKKPVPIIYCNRRTGKCQRM 1917 (insect) AP00995 A58718, Carnocin GSEIQPR1918 UI49 (bacteria) AP01002 AAC18827, KSWSLCTPGCARTGSFNSYCC 1919Mutacin III (mutacin 1140, bacteria) AP00987 ABI74601, ArasinSRWPSPGRPRPFPGRPKPIFRPRPCN 1920 1 (Crustacea) CYAPPCPCDRW AP01000CAA63706, GSGVIPTISHECHMNSFQFVFTCCS 1921 variacin (lantibiotic, class Ibacteriocin, bacteria) AP00361 O15946, Lebocin 4DLRFWNPREKLPLPTLPPFNPKPIYI 1922 (insect, silk moth) DMGNRY AP00343O16825, Andropin VFIDILDKMENAIHKAAQAGIGIAK 1923 (insect, fruit fly)PIEKMILPK AP00417 O17513, SIGTAVKKAVPIAKKVGKVAIPIAK 1924 Ceratotoxin DAVLSVVGQLVG (insect, fly) AP00435 O18494, Styelin CGWFGKAFRSVSNFYKKHKTYIHA 1925 (sea squirt, GLSAATLL tunicate, XXA)AP00330 O18495, Styelin D GWLRKAAKSVGKFYYKHKYYIKA 1926 (Sea squirt,AWQIGKHAL tunicate, XXA) AP00331 O18495, Styelin EGWLRKAAKSVGKFYYKHKYYIKA 1927 (Sea squirt, AWKIGRHAL tunicate, XXA)AP01001 O54329, Mutacin II NRWWQGVVPTVSYECRMNSWQH 1928 (lantibiotic,VFTCC mutacin H-29B, J- T8, class I bacteriocin, bacteria) AP00342O81338, AKCIKNGKGCREDQGPPFCCSGFC 1929 Antimicrobial YRQVGWARGYCKNRpeptide 1 (plant) AP00373 O96059, Moricin 2 AKIPIKAIKTVGKAVGKGLRAINIA1930 (insect) STANDVFNFLKPKKRKH AP00449 P01190, SYSMEHFRWGKPV 1931Melanotropin alpha (Alpha-MSH) AP00187 P01376, VVCACRRALCLPRERRAGFCRIRG1932 CORTICOSTATIN RIHPLCCRR III (MCP-1, rabbit neutrophil peptide 1,NP-1) (animal defensin, alpha- defensin, rabbit) AP00188 P01377,VVCACRRALCLPLERRAGFCRIRG 1933 CORTICOSTATIN RIHPLCCRR IV (MCP-2, rabbitneutrophil defensin 2, NP-2, animal defensin, rabbit) AP00049 P01505,Bombinin GIGALSAKGALKGLAKGLAEHFAN 1934 (toad) AP00139 P01507, CecropinKWKLFKKIEKVGQNIRDGIIKAGP 1935 A (insect, ZZHa) AVAVVGQATQIAK AP00128P01509, Cecropin KWKIFKKIEKVGRNIRNGIIKAGPA 1936 B (insect, silkVAVLGEAKAL moth) AP00131 P01511, Cecropin WNPFKELERAGQRVRDAIISAGPA 1937D (insect, moth) VATVAQATALAK AP00136 P01518, Crabrolin FLPLILRKIVTAL1938 (insect, XXA) AP00183 P04142, Cecropin RWKIFKKIEKMGRNIRDGIVKAGP1939 B (insect) AIEVLGSAKAI AP00448 P04205, INLKAIAALAKKLL 1940Mastoparan M (MP-M, insect, XXA) AP00234 P06833,SDEKASPDKHHRFSLSRYAKLANR 1941 Seminalplasmin LANPKLLETFLSKWIGDRGNRSV(SPLN, calcium transporter inhibitor, caltrin, cow) AP00314 P07466,Rabbit VFCTCRGFLCGSGERASGSCTINGV 1942 neutrophil peptide RHTLCCRR 5(NP-5, animal defensin, alpha- defensin) AP00189 P07467, RabbitVSCTCRRFSCGFGERASGSCTVNG 1943 neutrophil peptide VRHTLCCRR 4 (NP-4)AP00186 P07468, GRCVCRKQLLCSYRERRIGDCKIR 1944 CORTICOSTATIN GVRFPFCCPRII (Rabbit neutrophil peptide 3b (NP-3b, rabbit) AP00185 P07469,ICACRRRFCPNSERFSGYCRVNGA 1945 CORTICOSTATIN RYVRCCSRR I (rabbit) AP00217P07469, Rabbit GICACRRRFCPNSERFSGYCRVNG 1946 neutrophil defensinARYVRCCSRR 3a (NP-3a, animal defensin, alpha- defensin) AP00067 P07493,SKITDILAKLGKVLAHV 1947 Bombolitin II (insect, bee) AP00068 P07494,IKIMDILAKLGKVLAHV 1948 Bombolitin III (insect, bee) AP00069 P07495,INIKDILAKLVKVLGHV 1949 Bombolitin IV (insect, bee) AP00070 P07496,INVLGILGLLGKALSHL 1950 Bombolitin V (insect, bee) AP00236 P07504,Pyrularia KSCCRNTWARNCYNVCRLPGTISR 1951 thionin (Pp-TH,EICAKKCDCKIISGTTCPSDYPK plant) AP00230 P08375, SarcotoxinGWLKKIGKKIERVGQHTRDATIQG 1952 IA (insect, flesh LGIAQQAANVAATAR AP00231P08376, Sarcotoxin GWLKKIGKKIERVGQHTRDATIQV 1953 IB (insect, fleshIGVAQQAANVAATAR AP00232 P08377, Sarcotoxin GWLRKIGKKIERVGQHTRDATIQV 1954IC (insect, flesh LGIAQQAANVAATAR AP00066 P10521, IKITTMLAKLGKVLAHV 1955Bombolitin I (insect, bee) AP00206 P10946, LantibioticWKSESLCTPGCVTGALQTCFLQTL 1956 subtilin (class I TCNCKISK bacteriocin,bacteria) AP00312 P11477, Cryptdin-2 LRDLVCYCRARGCKGRERMNGTC 1957 (Crp2,animal RKGHLLYMLCCR defensin, alpha, mouse) AP00205 P13068, Nisin AITSISLCTPGCKTGALMGCNMKTA 1958 (lantibiotic, class I TCHCSIHVSKbacteriocin, bacteria) AP00215 P14214, RWCFRVCYRGICYRKCR 1959Tachyplesin II (crabs, Crustacea) AP00212 P14216, RRWCFRVCYKGFCYRKCR1960 Polyphemusin II (crabs, Crustacea, XXA, ZZHa. Derivatives: T22)AP00134 P14661, Cecropin SWLSKTAKKLENSAKKRISEGIAIA 1961 P1 (pig) IQGGPRAP00011 P14662, WNPFKELERAGQRVRDAVISAAPA 1962 Bactericidin B2VATVGQAAAIARG (insect) AP00032 P14663, WNPFKELERAGQRVRDAIISAGPA 1963Bactericidin B-3 VATVGQAAAIARG (insect) AP00033 P14664,WNPFKELERAGQRVRDAIISAAPA 1964 Bactericidin B-4 VATVGQAAAIARG (insect)AP00034 P14665, WNPFKELERAGQRVRDAVISAAA 1965 Bactericidin B-5PVATVGQAAAIARG (insect) AP00125 P14666, Cecropin RWKIFKKIEKVGQNIRDGIVKAGP1966 (insect, silk moth) AVAVVGQAATI AP00002 P15450,YVPLPNVPQPGRRPFPTFPGQGPFN 1967 ABAECIN (insect, PKIKWPQGY honeybee)AP00505 P15516, human DSHAKRHHGYKRKFHEKHHSHRGY 1968 Histatin 5 (ZZHs;derivatives Dh-5) AP00520 P15516, human DSHAKRHHGYKRKFHEKHHSHRG 1969Histatin 3 YRSNYLYDN AP00523 P15516, human KFHEKHHSHRGY 1970 Histatin 8AP00226 P17722, Royalisin VTCDLLSFKGQVNDSACAANCLSL 1971 (insect,honeybee) GKAGGHCEKVGCICRKTSFKDLW DKRF AP00213 P18252, KWCFRVCYRGICYRKCR1972 Tachyplesin III (horseshoe crabs, Crustacea) AP00233 P18312,Sarcotoxin GWIRDFGKRIERVGQHTRDATIQTI 1973 ID (insect, fleshAVAQQAANVAATLKG AP00207 P19578, Lantibiotic TAGPAIRASVKQCQKTLKATRLFT1974 PEP5 (class I VSCKGKNGCK bacteriocin, bacteria) AP00009 P19660,RFRPPIRRPPIRPPFYPPFRPPIRPPIF 1975 BACTENECIN 5 PPIRPPFRPPLGPFP (bac5,cow cathelicidin) AP00010 P19661, RRIRPRPPRLPRPRPRPLPFPRPGPR 1976BACTENECIN 7 PIPRPLPFPRPGPRPIPRPLPFPRPGP (bac7, cow RPIPRPLcathelicidin) AP00200 P21564, LKLKSIVSWAKKVL 1977 Mastoparan B (MP-B,insect, XXA) AP00005 P21663, Andropin VFIDILDKVENAIHNAAQVGIGFAK 1978(insect, fly) PFEKLINPK AP00008 P22226, Cyclic RLCRIVVIRVCR 1979dodecapeptide (cow cathelicidin) AP01205 P23826, Lactocin SSTPVLASVAVSMELLPTASVLYSD 1980 (XXD3, bacteria) VAGCFKYSAKHHC AP00239P24335, XPF (the GWASKIGQTLGKIAKVGLKELIQPK 1981 xenopsin precursorfragment, African clawed frog) AP00235 P25068, BovineNPVSCVRNKGICVPIRCPGSMKQIG 1982 tracheal TCVGRAVKCCRKK antimicrobialpeptide (TAP, cow) AP00418 P25230, CAP18 GLRKRLRKFRNKIKEKLKKIGQKIQ 1983(rabbit cathelicidin, GFVPKLAPRTDY BBL) AP00203 P25403, Mj-AMP1QCIGNGGRCNENVGPPYCCSGFCL 1984 (MjAMP1, plant RQPGQGYGYCKNR defensin)AP00202 P25404, Mj-AMP2 CIGNGGRCNENVGPPYCCSGFCLR 1985 (MjAMP2, plantQPNQGYGVCRNR defensin) AP00138 P28310, Cryptdin-3LRDLVCYCRKRGCKRRERMNGTC 1986 (Crp3, animal RKGHLMYTLCCR defensin, alpha,mouse) AP00184 P28794, MBP-1 RSGRGECRRQCLRRHEGQPWETQ 1987 (plant)ECMRRCRRRG AP00050 P29002, Bombinin- GIGASILSAGKSALKGLAKGLAEHF 1988 likepeptide 1 AN (BLP-1, toad) AP00051 P29003, Bombinin-GIGSAILSAGKSALKGLAKGLAEHF 1989 like peptide 2 AN (BLP-2, toad) AP00052P29004, Bombinin- GIGAAILSAGKSALKGLAKGLAEHF 1990 like peptide 3 (BLP-3,XXA, toad) AP00053 P29005, Bombinin- GIGAAILSAGKSIIKGLANGLAEHF 1991 likepeptide 4 (BLP-4, toad) AP00634 P29430, Pediocin KYYGNGVTCGKHSCSVDWGKATT1992 PA-1/AcH CIINNGAMAWATGGHQGNHKC (PedPA1, class IIA bacteriocin,bacteria) AP00204 P29559, Nisin Z ITSISLCTPGCKTGALMGCNMKTA 1993(lantibiotic, class I TCNCSIHVSK bacteriocin, bacteria) AP00130 P29561,Cecropin GWLKKLGKRIERIGQHTRDATIQG 1994 C (insect, fly) LGIAQQAANVAATARAP00001 P31107, GLWSKIKEVGKEAAKAAAKAAGK 1995 ADENOREGULIN AALGAVSEAV(Dermaseptin B2, Dermaseptin-B2, DRS-B2, DRS B2, frog) AP00228 P31529,Sapecin B LTCEIDRSLCLLHCRLKGYLRAYCS 1996 (insect, flesh fly) QQKVCRCVQAP00229 P31530, Sapecin C ATCDLLSGIGVQHSACALHCVFRG 1997 (insect, fleshfly) NRGGYCTGKGICVCRN AP00218 P32195, Protegrin RGGRLCYCRRRFCICV 1998 2(PG-2, pig cathelicidin) AP00219 P32196, Protegrin RGGGLCYCRRRFCVCVGR1999 3 (PG-3, pig cathelicidin) AP00073 P32412, Brevinin-FLPLLAGLAANFLPKIFCKITRKC 2000 1E (frog) AP00080 P32414,GIFSKLGRKKIKNLLISGLKNVGKE 2001 Esculentin-1 (frog) VGMDVVRTGIDIAGCKIKGECAP00074 P32423, Brevinin-1 FLPVLAGIAAKVVPALFCKITKKC 2002 (frog) AP00075P32424, Brevinin-2 GLLDSLKGFAATAGKGVLQSLLST 2003 (frog) ASCKLAKTCAP00175 P34084, Macaque DSHEERHHGRHGHHKYGRKFHEK 2004 histatin(M-Histatin HHSHRGYRSNYLYDN 1, primate, monkey) AP00006 P35581,Apidaecin GNNRPVYIPQPRPPHPRI 2005 IA (insect, honeybee) AP00007 P35581,Apidaecin GNNRPVYIPQPRPPHPRL 2006 IB (insect, honeybee) AP00414 P36190,SIGSALKKALPVAKKIGKIALPIAK 2007 Ceratotoxin A AALP (insect, fly) AP00415P36191, SIGSAFKKALPVAKKIGKAALPIAK 2008 Ceratotoxin B AALP (insect, fly)AP00172 P36193, Drosocin GKPRPYSPRPTSHPRPIRV 2009 (insect) AP00170P37362, VDKGSYLPRPTPPRPIYNRN 2010 Pyrrhocoricin (insect) AP00635 P38577,KYYGNGVHCTKSGCSVNWGEAAS 2011 Mesentericin Y105 AGIHRLANGGNGFW (MesY105,class IIA bacteriocin, bacteria) AP00636 P38579, AISYGNGVYCNKEKCWVNKAENK2012 Carnobacteriocin QAITGIVIGGWASSLAGMGH BM1 (CnbBM1, PiscV1b, classIIA bacteriocin, bacteria) AP00209 P39080, PeptideGVLSNVIGYLKKLGTGALNAVLKQ 2013 PGQ (frog) AP00513 P39084, RanalexinFLGGLIKIVPAMICAVTKKC 2014 (frog) AP00071 P40835, Brevinin-FLPAIFRMAAKVVPTIICSITKKC 2015 1EA (frog) AP00072 P40836, Brevinin-VIPFVASVAAEMQHVYCAASRKC 2016 1EB (frog) AP00076 P40837, Brevinin-GILDTLKNLAISAAKGAAQGLVNK 2017 2EA (frog) ASCKLSGQC AP00077 P40838,Brevinin- GILDTLKNLAKTAGKGALQGLVK 2018 2EB (frog) MASCKLSGQC AP00078P40839, Brevinin- GILLDKLKNFAKTAGKGVLQSLLN 2019 2EC (frog) TASCKLSGQCAP00079 P40840, Brevinin- GILDSLKNLAKNAGQILLNKASCK 2020 2ED (frog) LSGQCAP00081 P40843, GIFSKLAGKKIKNLLISGLKNVGKE 2021 Esculentin-1AVGMDVVRTGIDIAGCKIKGEC (frog) AP00082 P40844, GIFSKLAGKKLKNLLISGLKNVGK2022 Esculentin-1B EVGMDVVRTGIDIAGCKIKGEC (frog) AP00083 P40845,GILSLVKGVAKLAGKGLAKEGGKF 2023 Esculentin-2A GLELIACKIAKQC (frog) AP00084P40846, GIFSLVKGAAKLAGKGLAKEGGKF 2024 Esculentin-2B GLELIACKIAKQC(ES2B_RANES, frog) AP00299 P46156, Chicken GRKSDCFRKSGFCAFLKCPSLTLIS2025 gallinacin 1 (Gal 1, GKCSRFYLCCKRIW avian beta- defensin, bird)AP00300 P46157, Gallinacin GRKSDCFRKNGFCAFLKCPYLTLIS 2026 1 alpha (avianbeta- GKCSRFHLCCKRIW defensin, Bird), AP00298 P46158, ChickenLFCKGGSCHFGGCPSHLIKVGSCFG 2027 gallinacin 2 (Gal 2, FRSCCKWPWNA avianbeta- defensin, bird) AP00037 P46160, Beta- VRNHVTCRINRGFCVPIRCPGRTRQ2028 defensin 2 (cow) IGTCFGPRIKCCRSW AP00038 P46161, Beta-QGVRNHVTCRINRGFCVPIRCPGR 2029 defensin 3 (cow) TRQIGTCFGPRIKCCRSWAP00039 P46162, Beta- QRVRNPQSCRWNMGVCIPFLCRV 2030 defensin 4 (cow)GMRQIGTCFGPRVPCCRR AP00040 P46163, Beta- QVVRNPQSCRWNMGVCIPISCPGN 2031defensin 5 (cow) MRQIGTCFGPRVPCCRRW AP00041 P46164, Beta-QGVRNHVTCRIYGGFCVPIRCPGR 2032 defensin 6 (cow) TRQIGTCFGRPVKCCRRWAP00042 P46165, Beta- QGVRNFVTCRINRGFCVPIRCPGHR 2033 defensin 7 (cow)RQIGTCLGPRIKCCR AP00043 P46166, Beta- VRNFVTCRINRGFCVPIRCPGHRRQ 2034defensin 8 (cow) IGTCLGPQIKCCR AP00044 P46167, Beta-QGVRNFVTCRINRGFCVPIRCPGHR 2035 defensin 9 (cow) RQIGTCLAPQIKCCR AP00045P46168, Beta- QGVRSYLSCWGNRGICLLNRCPGR 2036 defensin 10 (cow)MRQIGTCLAPRVKCCR AP00046 P46169, Beta- GPLSCRRNGGVCIPIRCPGPMRQIG 2037defensin 11 (cow) TCFGRPVKCCRSW AP00048 P46171, BovineSGISGPLSCGRNGGVCIPIRCPVPM 2038 beta-defensin 13 RQIGTCFGRPVKCCRSW (cow)AP00350 P48821, Enbocin PWNIFKEIERAVARTRDAVISAGPA 2039 (insect, moth)VRTVAAATSVAS AP00173 P49112, GNCP-2 RCICTTRTCRFPYRRLGTCLFQNRV 2040(Guinea pig YTFCC neutrophil cationic peptide 2) AP00369 P49930, PMAP-23RIIDLLWRVRRPQKPKFVTVWVR 2041 (PMAP23, pig cathelicidin) AP00370 P49931,PMAP-36 VGRFRRLRKKTRKRLKKIGKVLK 2042 (PMAP36, pig WIPPIVGSIPLGCGcathelicidin) AP00371 P49932, PMAP-37 GLLSRLRDFLSDRGRRLGEKIERIG 2043(PMAP37, pig QKIKDLSEFFQS cathelicidin) AP00220 P49933, ProtegrinRGGRLCYCRGWICFCVGR 2044 4 (PG-4, pig cathelicidin) AP00221 P49934,Protegrin RGGRLCYCRPRFCVCVGR 2045 5 (PG-5, pig cathelicidin) AP00346P50720, Hyphancin RWKIFKKIERVGQNVRDGIIKAGP 2046 IIID (Fall AIQVLGTAKALwebworm, insect) AP00347 P50721, Hyphancin RWKFFKKIERVGQNVRDGLIKAGP 2047IIIE (Fall AIQVLGAAKAL webworm, insect) AP00348 P50722, HyphancinRWKVFKKIEKVGRNIRDGVIKAGP 2048 IIIF (Fall AIAVVGQAKAL webworm, insect)AP00349 P50723, Hyphancin RWKVFKKIEKVGRHIRDGVIKAGP 2049 IIIG (FallAITVVGQATAL webworm, insect) AP00281 P51473, mCRAMPGLLRKGGEKIGEKLKKIGQKIKNFF 2050 (mouse QKLVPQPEQ cathelicidin;derivatives: CRAMP 18) AP00366 P54228, BMAP-27 GRFKRFRKKFKKLFKKLSPVIPLLH2051 (BMAP27, cow LG cathelicidin, ZZHs, derivatives BMAP- 18 andBMAP-15) AP00367 P54229, BMAP-28 GGLRSLGRKILRAWKKYGPIIVPIIR 2052(BMAP28, cow IG cathelicidin) AP00450 P54230, Cyclic RICRIIFLRVCR 2053dodecapeptide (sheep cathelicidin) AP00359 P54684, LebocinDLRFLYPRGKLPVPTPPPFNPKPIYI 2054 ½ (insect, silk DMGNRY moth) AP00360P55796, Lebocin 3 DLRFLYPRGKLPVPTLPPFNPKPIYI 2055 (insect, silk moth)DMGNRY AP00307 P55897, Buforin I AGRGKQGGKVRAKAKTRSSRAGL 2056 (toad)QFPVGRVHRLLRKGNY AP00308 P55897, Buforin II TRSSRAGLQFPVGRVHRLLRK 2057(toad) AP00240 P56226, Caerin 1.1 GLLSVLGSVAKHVLPHVVPVIAEHL 2058 (frog,ZZHa) AP00241 P56227, Caerin 1.2 GLLGVLGSVAKHVLPHVVPVIAEHL 2059 (frog)AP00242 P56228, Caerin 1.3 GLLSVLGSVAQHVLPHVVPVIAEHL 2060 (frog) AP00243P56229, Caerin 1.4 GLLSSLSSVAKHVLPHVVPVIAEHL 2061 (frog) AP00244 P56230,Caerin 1.5 GLLSVLGSVVKHVIPHVVPVIAEHL 2062 (frog) AP00245 P56231, Caerin1.6 GLFSVLGAVAKHVLPHVVPVIAEK 2063 (frog) AP00246 P56232, Caerin 1.7GLFKVLGSVAKHLLPHVAPVIAEK 2064 (frog) AP00249 P56233, Caerin 2.1GLVSSIGRALGGLLADVVKSKGQPA 2065 (frog) AP00250 P56234, Caerin 2.2GLVSSIGRALGGLLADVVKSKEQPA 2066 (frog) AP00251 P56236, Caerin 2.4GLVSSIGKALGGLLADVVKTKEQPA 2067 (frog) AP00252 P56236, Caerin 2.5GLVSSIGRALGGLLADVVKSKEQPA 2068 (frog) AP00253 P56238, Caerin 3.1GLWQKIKDKASELVSGIVEGVK 2069 (frog) AP00254 P56238, Caerin 3.2GLWEKIKEKASELVSGIVEGVK 2070 (frog) AP00255 P56240, Caerin 3.3GLWEKIKEKANELVSGIVEGVK 2071 (frog) AP00256 P56241, Caerin 3.4GLWEKIREKANELVSGIVEGVK 2072 (frog) AP00257 P56242, Caerin 4.1GLWQKIKSAAGDLASGIVEGIKS 2073 (frog) AP00258 P56243, Caerin 4.2GLWQKIKSAAGDLASGIVEGIKS 2074 (frog) AP00259 P56244, Caerin 4.3GLWQKIKNAAGDLASGIVEGIKS 2075 (frog) AP00434 P56249, Frenatin 3GLMSVLGHAVGNVLGGLFKS 2076 (frog) AP00272 P56386, MurineDQYKCLQHGGFCLRSSCPSNTKLQ 2077 beta-defensin 1 GTCKPDKPNCCKS (mBD-1,mouse) AP00368 P56425, BMAP-34 GLFRRLRDSIRRGQQKILEKARRIG 2078 (BMAP34,cow ERIKDIFRG cathelicidin) AP00273 P56685, ButhininSIVPIRCRSNRDCRRFCGFRGGRCT 2079 (Sahara scorpion) YARQCLCGY AP00282P56872, SIPCGESCVFIPCTVTALLGCSCKSK 2080 Cyclopsychotride VCYKN A (CPT,plant cyclotides, XXC) AP00094 P56917, Temporin FLPLIGRVLSGIL 2081 A(XXA, frog) AP00096 P56918, Temporin LLPILGNLLNGLL 2082 C (XXA, frog)AP00097 P56920, Temporin VLPIIGNLLNSLL 2083 E (XXA, frog) AP00098P56921, Temporin FLPLIGKVLSGIL 2084 F (XXA, frog) AP00100 P56923,Temporin LLPNLLKSLL 2085 K (XXA, frog) AP00295 P56928, eNAP-2EVERKHPLGGSRPGRCPTVPPGTF 2086 (horse) GHCACLCTGDASEPKGQKCCSN AP00101P57104, Temporin FVQWFSKFLGRIL 2087 L (XXA, frog) AP00095 P79874,Temporin LLPIVGNLLKSLL 2088 B (XXA, frog) AP00099 P79875, TemporinFFPVIGRILNGIL 2089 G (XXA, frog) AP00413 P80032, SLQGGAPNFPQPSQQNGGWQVSP2090 Coleoptericin DLGRDDKGNTRGQIEIQNKGKDH (insect)DFNAGWGKVIRGPNKAKPTWHVG GTYRR AP00396 P80054, PR-39RRRPRPPYLPRPRPPPFFPPRLPPRIP 2091 (PR39, pig PGFPPRFPPRFP cathelicidin)AP00182 P80154, Insect GFGCPLDQMQCHRHCQTITGRSGG 2092 defensinYCSGPLKLTCTCYR AP00444 P80223, GICACRRRFCLNFEQFSGYCRVNG 2093Corticostatin VI ARYVRCCSRR (CS-VI) (animal defensin, rabbit) AP00208P80230, Peptide RADTQTYQPYNKDWIKEKIYVLLR 2094 3910 (pig) RQAQQAGKAP00157 P80277, ALWKTMLKKLGTMALHAGKAAL 2095 Dermaseptin-S1 GAAADTISQGTQ(Dermaseptin S1, DRS S1, DRS-S1, frog) AP00158 P80278,ALWFTMLKKLGTMALHAGKAAL 2096 Dermaseptin-S2 GAAANTISQGTQ (Dermaseptin S2,DRS S2, DRS-S2, frog) AP00159 P80279, ALWKNMLKGIGKLAGKAALGAV 2097Dermaseptin-S3 KKLVGAES (Dermaseptin S3, DRS S3, DRS-S3, frog) AP00160P80280, ALWMTLLKKVLKAAAKALNAVL 2098 Dermaseptin-S4 VGANA (DermaseptinS4, DRS S4, DRS-S4, frog) AP00161 P80281, GLWSKIKTAGKSVAKAAAKAAVK 2099Dermaseptin-S5 AVTNAV (Dermaseptin S5, DRS S5, DRS-S5, frog) AP00293P80282, AMWKDVLKKIGTVALHAGKAAL 2100 Dermaseptin-B1 GAVADTISQ (DRS-B1,DRS B1, frog) AP00264 P80389, Chicken GRKSDCFRKSGFCAFLKCPSLTLIS 2101Heterophil Peptide GKCSRFYLCCKRIR 1 (CHP1, bird, animal) AP00265 P80390,Chicken GRKSDCFRKNGFCAFLKCPYLTLIS 2102 Heterophil Peptide GLCSFHLC 2(CHP2, bird, animal) AP00266 P80391, Turkey GKREKCLRRNGFCAFLKCPTLSVIS2103 Heterophil Peptide GTCSRFQVCC 1 (THP1, turkey) AP00267 P80392,Turkey LFCKRGTCHFGRCPSHLIKVGSCFG 2104 Heterophil Peptide FRSCCKWPWDA 2(THP2, bird, anaimal) AP00269 P80393, Turkey LSCKRGTCHFGRCPSHLIKGSCSGG2105 Heterophil Peptide 3 (THP3, bird, animal) AP00085 P80395, Gaegurin-SLFSLIKAGAKFLGKNLLKQGACY 2106 1 (Gaegurin 1, AACKASKQC frog) AP00086P80396, Gaegurin- GIMSIVKDVAKNAAKEAAKGALST 2107 2 (Gaegurin 2, LSCKLAKTCfrog) AP00087 P80397, Gaegurin- GIMSIVKDVAKTAAKEAAKGALST 2108 3(Gaegurin 3, LSCKLAKTC frog) AP00089 P80399, Gaegurin-FLGALFKVASKVLPSVFCAITKKC 2109 5 (Gaegurin 5, frog) AP00090 P80400,Gaegurin- FLPLLAGLAANFLPTIICKISYKC 2110 6 (Gaegurin 6, frog) AP00362P80408, VDKPDYRPRPRPPNM 2111 Metalnikowin I (insect) AP00363 P80409,VDKPDYRPRPWPRPN 2112 Metalnikowin IIA (insect) AP00364 P80410,VDKPDYRPRPWPRNMI 2113 Metalnikowin IIB (insect) AP00365 P80411,VDKPDYRPRPWPRPNM 2114 Metalnikowin III (insect) AP00632 P80569,Piscicolin KYYGNGVSCNKNGCTVDWSKAIG 2115 126/PiscicocinIIGNNAAANLTTGGAAGWNKG Via (PiscV1a, Pisc126, class IIA bacteriocin,bacteria) AP01003 P80666, Mutacin FKSWSFCTPGCAKTGSFNSYCC 2116 B-Ny266(bacteria) AP00276 P80710, Clavanin VFQFLGKIIHHVGNFVHGFSHVF 2117 A(urochordates, sea squirts, and sea pork, tunicate) AP00277 P80711,Clavanin VFQFLGRIIHHVGNFVHGFSHVF 2118 B (Sea squirt, tunicate) AP00278P80712, Clavanin VFHLLGKIIHHVGNFVYGFSHVF 2119 C (Sea squirt, tunicate)AP00279 P80713, Clavanin AFKLLGRIIHHVGNFVYGFSHVF 2120 D (Sea squirt,tunicate) AP00280 P80713, Clavanin LFKLLGKIIHHVGNFVHGFSHVF 2121 D (Seasquirt, tunicate) AP00294 P80930, eNAP-1 DVQCGEGHFCHDQTCCRASQGGA 2122(horse) CCPYSQGVCCADQRHCCPVGF AP00400 P80952, SkinYPPKPESPGEDASPEEMNKYLTAL 2123 peptide tyrosine- RHYINLVTRQRY tyrosine(skin- PYY, SPYY, frog) AP00091 P80954, Rugosin AGLLNTFKDWAISIAKGAGKGVLTT 2124 (frog) LSCKLDKSC AP00092 P80955, Rugosin BSLFSLIKAGAKFLGKNLLKQGAQY 2125 (frog) AACKVSKEC AP00093 P80956, Rugosin CGILDSFKQFAKGVGKDLIKGAAQG 2126 (frog) VLSTMSCKLAKTC AP00392 P81056,Penaeidin- YRGGYTGPIPRPPPIGRPPLRLVVC 2127 1 (shrimp,ACYRLSVSDARNCCIKFGSCCHLVK Crustacea) AP00393 P81057, Penaeidin-YRGGYTGPIPRPPPIGRPPFRPVCN 2128 2a (shrimp, ACYRLSVSDARNCCIKFGSCCHLVKCrustacea) AP00394 P81058, Penaeidin- QVYKGGYTRPIPRPPPFVRPLPGGP 2129 3a(shrimp, IGPYNGCPVSCRGISFSQARSCCSR Crustacea) LGRCCHVGKGYS AP00247P81251, Caerin 1.8 GLFKVLGSVAKHLLPHVVPVIAEK 2130 (frog) AP00248 P81252,Caerin 1.9 GLFGVLGSIAKHVLPHVVPVIAEK 2131 (frog, ZZHa) AP00126 P81417,Cecropin GGLKKLGKKLEGVGKRVFKASEK 2132 A (insect, ALPVAVGIKALG mosquito)AP00169 P81437, Formaecin GRPNPVNTKPTPYPRL 2133 2 (insect, ants) AP00168P81438, Formaecin GRPNPVNNKPTPHPRL 2134 1 (insect, ants) AP00296 P81456,Fabatin-1 LLGRCKVKSNRFHGPCLTDTHCST 2135 (plant defensin)VCRGEGYKGGDCHGLRRRCMCLC AP00297 P81457, Fabatin-2LLGRCKVKSNRFNGPCLTDTHCST 2136 (plant defensin) VCRGEGYKGGDCHGLRRRCMCLCAP01215 P81463, European FVPYNPPRPYQSKPFPSFPGHGPFN 2137 bumblebeeabaecin PKIQWPYPLPNPGH (insect) AP01214 P81464, ApidaecinGNRPVYIPPPRPPHPRL 2138 (insect) AP00440 P81465, defensinVTCFCRRRGCASRERHIGYCRFGN 2139 HANP-1 (hamster) TIYRLCCRR AP00441 P81466,defensin CFCKRPVCDSGETQIGYCRLGNTF 2140 HANP-2 (hamster) YRLCCRQ AP00442P81467, defensin VTCFCRRRGCASRERLIGYCRFGN 2141 HANP-3 (hamster)TIYGLCCRR AP00439 P81468, defensin VTCFCKRPVCDSGETQIGYCRLGN 2142 HANP-4(hamster) TFYRLCCRQ AP00328 P81469, Styelin A GFGKAFHSVSNFAKKHKTA 2143(Sea squirt, tunicate, XXA) AP00329 P81470, Styelin BGFGPAFHSVSNFAKKHKTA 2144 (Sea squirt, tunicate, XXA) AP00492 P81474,Misgurin RQRVEELSKFSKKGAAARRRK 2145 (fish) AP00165 P81485,ALWKNMLKGIGKLAGQAALGAV 2146 Dermaseptin-B3 KTLVGAE (Dermaseptin B3,DRS-B3, DRS B3, frog) AP00163 P81486, ALWKDILKNVGKAAGKAVLNTVT 2147Dermaseptin-B4 DMVNQ (Dermaseptin B4, DRS-B4, DRS B4, DRS-TR1, IRP,frog) AP00162 P81487, GLWNKIKEAASKAAGKAALGFVN 2148 Dermaseptin-B5 EMV(Dermaseptin B5, DRS-B5, DRS B5, frog) AP00164 P81488,ALWKTIIKGAGKMIGSLAKNLLGS 2149 Dermaseptin-B9 QAQPES (Dermaseptin B9,DRS-B9, DRS DRG3, frog) AP00167 P81565, Phylloxin GWMSKIASGIGTFLSGMQQ2150 (phylloxin-B1, PLX-B1, XXA, frog) AP00291 P81568, DefensinMFFSSKKCKTVSKTFRGPCVRNAN 2151 D5 (So-D5) (plant defensin) AP00290P81569, Defensin MFFSSKKCKTVSKTFRGPCVRNA 2152 D4 (So-D4) (plantdefensin) AP00289 P81570, Defensin GIFSSRKCKTVSKTFRGICTRNANC 2153 D3(So-D3) (plant defensin) AP00288 P81572, Defensin TCESPSHKFKGPCATNRNCES2154 D1 (So-D1) (plant defensin) AP00292 P81573, DefensinGIFSSRKCKTPSKTFKGYCTRDSNC 2155 D7 (So-D7) (plant DTSCRYEGYPAGD defensin)AP00270 P81591, Pn-AMP QQCGRQASGRLCGNRLCCSQWGY 2156 (PnAMP, plantCGSTASYCGAGCQSQCRS defensin) AP00412 P81592, SLQPGAPNVNNKDQPWQVSPHISR2157 Acaloleptin A1 DDSGNTRTDINVQRHGENNDFEAG (insect)WSKVVRGPNKAKPTWHIGGTHRW AP00433 P81605, human SSLLEKGLDGAKKAVGGLGKLGK2158 Dermcidin (DCD- DAVEDLESVGKGAVHDVKDVLDSV 1) AP00332 P81612, MytilinA GCASRCKAKCAGRRCKGWASASF 2159 (Blue mussel) RGRCYCKCFRC AP00333 P81613,Mytilin B SCASRCKGHCRARRCGYYVSVLY 2160 (Blue mussel) RGRCYCKCLRC AP00334P81613, FFHHIFRGIVHVGKTIHKLVTG 2161 Moronecidin (fish) AP00351 P81835,Citropin GLFDVIKKVASVIGGL 2162 1.1 (amphibian, frog) AP00352 P81840,Citropin GLFDIIKKVASVVGGL 2163 1.2 (amphibian, frog) AP00353 P81846,Citropin GLFDIIKKVASVIGGL 2164 1.3 (amphibian, frog) AP00338 P81903,Histone PDPAKTAPKKGSKKAVTKA 2165 H2B-1(HLP-1) (fish) AP00271 P82018,ChBac5 RFRPPIRRPPIRPPFNPPFRPPVRPPF 2166 (Goat cathelicidin)RPPFRPPFRPPIGPFP AP00316 P82027, Uperin 2.1 GIVDFAKKVVGGIRNALGI 2167(amphibian, toad) AP00317 P82028, Uperin 2.2 GFVDLAKKVVGGIRNALGI 2168(amphibian, toad) AP00318 P82029, Uperin 2.3 GFFDLAKKVVGGIRNALGI 2169(amphibian, toad) AP00319 P82030, Uperin 2.4 GILDFAKTVVGGIRNALGI 2170(amphibian, toad) AP00320 P82031, Uperin 2.5 GIVDFAKGVLGKIKNVLGI 2171(amphibian, toad) AP00323 P82032, Uperin 3.1 GVLDAFRKIATVVKNVV 2172(amphibian, toad) AP00326 P82035, Uperin 4.1 GVGSFIHKVVSAIKNVA 2173(amphibian, toad) AP00321 P82039, Uperin 2.7 GIIDIAKKLVGGIRNVLGI 2174(amphibian, toad) AP00322 P82040, Uperin 2.8 GILDVAKTLVGKLRNVLGI 2175(amphibian, toad) AP00324 P82042, Uperin 3.5 GVGDLIRKAVSVIKNIV 2176(amphibian, toad) AP00325 P82042, Uperin 3.6 GVIDAAKKVVNVLKNLP 2177(amphibian, toad) AP00327 P82050, Uperin 7.1 GWFDVVKHIASAV 2178(amphibian, frog) AP00260 P82066, Maculatin GLFVGVLAKVAAHVVPAIAEHF 21791.1 (XXA, frog, ZZHa) AP00261 P82067, Maculatin GLFVGLAKVAAHNNPAIAEHFQA2180 1.2 (XXA, frog) AP00262 P82068, Maculatin GFVDFLKKVAGTIANVVT 21812.1 (frog) AP00263 P82069, Maculatin GLLQTIKEKLESLESLAKGIVSGIQA 2182 3.1(frog) AP00345 P82104, Caerin GLLSVLGSVAKHVLPHVVPVIAEKL 2183 1.10 (frog)AP00456 P82232, Brevinin- VNPIILGVLPKFVCLITKKC 2184 1T (frog) AP00459P82233, Brevinin- FITLLLRKFICSITKKC 2185 1TA (frog) AP00457 P82234,Brevinin- GLWETIKNFGKKFTLNILHKLKCKI 2186 2TC (frog) GGGC AP00458 P82235,Brevinin- GLWETIKNFGKKFTLNILHNLKCKI 2187 2TD (frog) GGGC AP00397 P82238,SGFVLKGYTKTSQ 2188 Salmocidin 2A (fish, trout) AP00398 P82239,AGFVLKGYTKTSQ 2189 Salmocidin 2B (fish, trout) AP00055 P82282, BombininIIGPVLGMVGSALGGLLKKI 2190 H1 (frog) AP00056 P82284, BombininLIGPVLGLVGSALGGLLKKI 2191 H4 (frog, XXA, XXD) AP00057 P82285, BombininIIGPVLGLVGSALGGLLKKI 2192 H5 (frog, XXD) AP00419 P82286, Bombinin-GIGASILSAGKSALKGFAKGLAEHF 2193 like peptides 2 AN (amphibian, toad)AP00137 P82293, Cryptdin-1 LRDLVCYCRTRGCKRRERMNGTC 2194 (Crp1, animalRKGHLMYTLCCR defensin, alpha, mouse) AP00443 P82317, defensinACYCRIPACLAGERRYGTCFYMGR 2195 RMAD-2 (monkey) VWAFCC AP00012 P82386,Aurein 1.1 GLFDIIKKIAESI 2196 (amphibian, frog) AP00014 P82388, Aurein2.1 GLLDIVKKVVGAFGSL 2197 (amphibian, frog) AP00015 P82389, Aurein 2.2GLFDIVKKVVGALGSL 2198 (amphibian, frog) AP00016 P82390, Aurein 2.3GLFDIVKKVVGAIGSL 2199 (XXA, amphibian, frog) AP00017 P82391, Aurein 2.4GLFDIVKKVVGTIAGL 2200 (XXA, amphibian, frog) AP00018 P82392, Aurein 2.5GLFDIVKKVVGAFGSL 2201 (XXA, amphibian, frog) AP00019 P82393, Aurein 2.6GLFDIAKKVIGVIGSL 2202 (XXA, amphibian, frog) AP00020 P82394, Aurein 3.1GLFDIVKKIAGHIAGSI 2203 (XXA, amphibian, frog) AP00021 P82395, Aurein 3.2GLFDIVKKIAGHIASSI 2204 (XXA, amphibian, frog) AP00022 P82396, Aurein 3.3GLFDIVKKIAGHIVSSI 2205 (XXA, amphibian, frog) AP00376 P82414, PonericinGWKDWAKKAGGWLKKKGPGMA 2206 G1 (ants) KAALKAAMQ AP00377 P82415, PonericinGWKDWLKKGKEWLKAKGPGIVK 2207 G2 (ants) AALQAATQ AP00378 P82416, PonericinGWKDWLNKGKEWLKKKGPGIMK 2208 G3 (ants) AALKAATQ AP00379 P82417, PonericinDFKDWMKTAGEWLKKKGPGILKA 2209 G4 (ants) AMAAAT AP00380 P82418, PonericinGLKDWVKIAGGWLKKKGPGILKA 2210 G5 (ants) AMAAATQ AP00381 P82419, PonericinGLVDVLGKVGGLIKKLLP 2211 G6 (ants) AP00382 P82420, PonericinGLVDVLGKVGGLIKKLLPG 2212 G7 (ants) AP00383 P82421, PonericinLLKELWTKMKGAGKAVLGKIKGLL 2213 L1 (ants) AP00384 P82422, PonericinLLKELWTKIKGAGKAVLGKIKGLL 2214 L2 (ants) AP00386 P82423, PonericinWLGSALKIGAKLLPSVVGLFKKKKQ 2215 W1 (ants) AP00387 P82424, PonericinWLGSALKIGAKLLPSVVGLFQKKKK 2216 W2 (ants) AP00388 P82425, PonericinGIWGTLAKIGIKAVPRVISMLKKK 2217 W3 (ants) KQ AP00389 P82426, PonericinGIWGTALKWGVKLLPKLVGMAQT 2218 W4 (ants) KKQ AP00390 P82427, PonericinFWGALIKGAAKLIPSVVGLFKKKQ 2219 W5 (ants) AP00391 P82428, PonericinFIGTALGIASAIPAIVKLFK 2220 W6 (ants) AP00303 P82651, Tigerinin-FCTMIPIPRCY 2221 1 (frog) AP00304 P82652, Tigerinin- RVCFAIPLPICH 2222 2(frog) AP00305 P82653, Tigerinin- RVCYAIPLPICY 2223 3 (frog) AP00301P82656, Hadrurin GILDTIKSIASKVWNSKTVQDLKR 2224 (scorpion)KGINWVANKLGVSPQAA AP00113 P82740, GLLSGLKKVGKHVAKNVAVSLMD 2225RANATUERIN 1T SLKCKISGDC (frog) AP00114 P82741, SMLSVLKNLGKVGLGFVACKINK2226 RANATUERIN 1 QC (Ranatuerin-1, frog) AP00115 P82742,GLFLDTLKGAAKDVAGKLEGLKC 2227 RANATUERIN 2 KITGCKLP (Ranatuerin-2, frog)AP00116 P82780, GFLDIINKLGKTFAGHMLDKIKCTI 2228 RANATUERIN 3 GTCPPSP(Ranatuerin-3, frog) AP00117 P82819, FLPFIARLAAKVFPSIICSVTKKC 2229RANATUERIN 4 (Ranatuerin-4, frog) AP00405 P82821, FISAIASMLGKFL 2230RANATUERIN 6 (frog) AP00406 P82822, FLSAIASMLGKFL 2231 RANATUERIN 7(frog) AP00407 P82823, FISAIASFLGKFL 2232 RANATUERIN 8 (frog) AP00408P82824, FLFPLITSFLSKVL 2233 RANATUERIN 9 (frog) AP00461 P82825,Brevinin- FLPMLAGLAASMVPKLVCLITKKC 2234 1LA (frog) AP00462 P82826,Brevinin- FLPMLAGLAASMVPKFVCLITKKC 2235 1LB (frog) AP00118 P82828,GILDSFKGVAKGVAKDLAGKLLD 2236 RANATUERIN KLKCKITGC 2La (Ranatuerin- 2La,frog) AP00119 P82829, GILSSIKGVAKGVAKNVAAQLLDT 2237 RANATUERIN LKCKITGC2Lb (Ranatuerin- 2Lb, frog) AP00109 P82830, Temporin- VLPLISMALGKLL 22381La (Temporin 1La, frog) AP00110 P82831, Temporin- NFLGTLINLAKKIM 22391Lb (Temporin 1Lb, frog) AP00111 P82832, Temporin- FLPILINLIHKGLL 22401Lc (Temporin 1Lc, frog) AP00463 P82833, Brevinin-FLPFIAGMAAKFLPKIFCAISKKC 2241 1BA (frog) AP00464 P82834, Brevinin-FLPAIAGMAAKFLPKIFCAISKKC 2242 1BB (frog) AP00465 P82835, Brevinin-FLPFIAGVAAKFLPKIFCAISKKC 2243 1BC (frog) AP00466 P82836, Brevinin-FLPAIAGVAAKFLPKIFCAISKKC 2244 1BD (frog) AP00467 P82837, Brevinin-FLPAIVGAAAKFLPKIFCVISKKC 2245 1BE (frog) AP00468 P82838, Brevinin-FLPFIAGMAANFLPKIFCAISKKC 2246 1BF (frog) AP00120 P82840,GLLDTIKGVAKTVAASMLDKLKC 2247 RANATUERIN 2B KISGC (Ranatuerin-2B, frog)AP00469 P82841, Brevinin- FLPIIAGVAAKVFPKIFCAISKKC 2248 1PA (frog)AP00460 P82842, Brevinin- FLPIIAGIAAKVFPKIFCAISKKC 2249 1PB (frog)AP00470 P82843, Brevinin- FLPIIASVAAKVFSKIFCAISKKC 2250 1PC (frog)AP00471 P82844, Brevinin- FLPIIASVAANVFSKIFCAISKKC 2251 1PD (frog)AP00472 P82845, Brevinin- FLPIIASVAAKVFPKIFCAISKKC 2252 1PE (frog)AP00121 P82847, GLMDTVKNVAKNLAGHMLDKLK 2253 RANATUERIN 2P CKITGC(Ranatuerin-2P, frog) AP00112 P82848, Temporin- FLPIVGKLLSGLL 2254 1P(Temporin 1P, frog) AP00452 P82871, Brevinin- FLPVVAGLAAKVLPSIICAVTKKC2255 1SY (frog) AP00122 P82875, SMLSVLKNLGKVGLGLVACKINK 2256Ranatuerin-1C QC (Ranatuerin 1C, frog) AP00514 P82876, Ranalexin-FLGGLMKAFPALICAVTKKC 2257 1Ca (frog) AP00515 P82877, Ranalexin-FLGGLMKAFPAIICAVTKKC 2258 1Cb (frog) AP00124 P82878,GLFLDTLKGAAKDVAGKLLEGLK 2259 Ranatuerin-2Ca CKIAGCKP (Ranatuerin 2Ca,frog) AP00123 P82879, GLFLDTLKGLAGKLLQGLKCIKAG 2260 Ranatuerin-2Cb CKP(Ranatuerin 2Cb, frog) AP00104 P82880, Temporin- FLPFLAKILTGVL 2261 1Ca(Temporin 1Ca, frog) AP00105 P82881, Temporin- FLPLFASLIGKLL 2262 1Cb(Temporin 1Cb, frog) AP00106 P82882, Temporin- FLPFLASLLTKVL 2263 1Cc(Temporin 1Cc, frog) AP00107 P82883, Temporin- FLPFLASLLSKVL 2264 1Cd(Temporin 1Cd, frog) AP00108 P82884, Temporin- FLPFLATLLSKVL 2265 1Ce(Temporin 1Ce, frog) AP00453 P82904, Brevinin- FLPAIVGAAGQFLPKIFCAISKKC2266 1SA (frog) AP00454 P82905, Brevinin- FLPAIVGAAGKFLPKIFCAISKKC 22671SB (frog) AP00455 P82906, Brevinin- FFPIVAGVAGQVLKKIYCTISKKC 2268 1SC(frog) AP00996 P82907, Lichenin ISLEICAIFHDN 2269 (bacteria) AP00302P82951, Hepcidin GCRFCCNCCPNMSGCGVCCRF 2270 (fish) AP00058 P83080,Maximin 1 GIGTKILGGVKTALKGALKELAST 2271 (toad) YAN AP00059 P83081,Maximin 2 GIGTKILGGVKTALKGALKELAST 2272 (toad) YVN AP00060 P83082,Maximin 3 GIGGKILSGLKTALKGAAKELAST 2273 (toad, ZZHa) YLH AP00061 P83083,Maximin 4 GIGGVLLSAGKAALKGLAKVLAE 2274 (toad) KYAN AP00062 P83084,Maximin 5 SIGAKILGGVKTFFKGALKELASTY 2275 (toad) LQ AP00063 P83085,Maximin 6 ILGPVISTIGGVLGGLLKNL 2276 (toad) AP00064 P83086, Maximin 7ILGPVLGLVGNALGGLIKNE 2277 (toad) AP00065 P83087, Maximin 8ILGPVLSLVGNALGGLLKNE 2278 (toad) AP00355 P83171,ANTAFVSSAHNTQKIPAGAPFNRN 2279 Ginkbilobin LRAMLADLRQNAAFAG (Chineseplant) AP00475 P83188, Pseudin 1 GLNTLKKVFQGLHEAIKLINNHVQ 2280 (frog)AP00476 P83189, Pseudin 2 GLNALKKVFQGIHEAIKLINNHVQ 2281 (frog) AP00477P83190, Pseudin 3 GINTLKKVIQGLHEVIKLVSNHE 2282 (frog) AP00478 P83191,Pseudin 4 GINTLKKVIQGLHEVIKLVSNHA 2283 (frog) AP00410 P83287,SKGKKANKDVELARG 2284 Oncorhyncin III (fish) AP00357 P83305, Japonicin-FFPIGVFCKIFKTC 2285 1 (amphibian, frog) AP00358 P83306, Japonicin-FGLPMLSILPKALCILLKRKC 2286 2 (amphibian, frog) AP00385 P83312,FKLGSFLKKAWKSKLAKKLRAKG 2287 Parabutoporin KEMLKDYAKGLLEGGSEEVPGQ(scorpion) AP00374 P83313, GKVWDWIKSTAKKLWNSEPVKEL 2288 Opistoporin 1KNTALNAAKNLVAEKIGATPS (scorpion) AP00375 P83314, GKVWDWIKSTAKKLWNSEPVKEL2289 Opistoporin 2 KNTALNAAKNFVAEKIGATPS (scorpion) AP00336 P83327,Histone AERVGAGAPVYL 2290 H2A (fish) AP00335 P83338, HistonePKRKSATKGDEPA 2291 H6-like protein (fish) AP00411 P83374,KAVAAKKSPKKAKKPAT 2292 Oncorhyncin II (fish) AP00999 P83375, Serracin-PDYHHGVRVL 2293 43 kDa subunit (bacteria) AP00284 P83376,SHQDCYEALHKCMASHSKPFSCS 2294 Dolabellanin B2 MKFHMCLQQQ (sea hare)AP00998 P83378, Serracin-P ALPKKLKYLNLFNDGFNYMGVV 2295 23 kDa subunit(bacteriocin, bacteria) AP00129 P83403, Cecropin GWLKKIGKKIERVGQNTRDATVK2296 (insect, moth) GLEVAQQAANVAATVR AP00127 P83413, CecropinRWKVFKKIEKVGRNIRDGVIKAAP 2297 A (insect, moth) AIEVLGQAKAL AP00372P83416, Virescein GKIPIGAIKKAGKAIGKGLRAVNIA 2298 (insect)STAHDVYTFFKPKKRH AP00356 P83427, Heliocin QRFIHPTYRPPPQPRRPVIMRA 2299(insect) AP00409 P83428, Locustin ATTGCSCPQCIIFDPICASSYKNGRR 2300(insect) GFSSGCHMRCYNRCHGTDYFQISK GSKCI AP00339 P83545,FFGWLIKGAIHAGKAIHGLIHRRRH 2301 Chrysophsin-1 (Red sea bream, madai)AP00340 P83546, FFGWLIRGAIHAGKAIHGLIHRRRH 2302 Chrysophsin-2 (Red seabream, madai) AP00341 P83547, FIGLLISAGKAIHDLIRRRH 2303 Chrysophsin-3(Red sea bream, madai) AP01004 P84763, Thuricin-S DWTAWSALVAAACSVELL2304 (bacteria) AP00553 P84868, Sesquin KTCENLADTY 2305 (plant, ZZHp)AP00132 Q06589, Cecropin GWLKKIGKKIERVGQHTRDATIQTI 2306 1 (insect, fly)AVAQQAANVAATAR AP00135 Q06590, Cecropin GWLKKIGKKIERVGQHTRDATIQTI 2307 2(insect fly) GVAQQAANVAATLK AP00416 Q17313, SLGGVISGAKKVAKVAIPIGKAVLP2308 Ceratotoxin C VVAKLVG (insect, fly) AP00171 Q24395,HRHQGPIFDTRPSPFNPNQPRPGPIY 2309 Metchnikowin (insect) AP00354 Q27023,Tenecin 1 VTCDILSVEAKGVKLNDAACAAH 2310 (insect) CLFRGRSGGYCNGKRVCVCRAP00401 Q28880, Lingual GFTQGVRNSQSCRRNKGICVPIRCP 2311 antimicrobialGSMRQIGTCLGAQVKCCRRK peptide (LAP, beta defensin, cow) AP00224 Q62713,RatNP-3 CSCRTSSCRFGERLSGACRLNGRIY 2312 (rat) RLCC AP00225 Q62714,RatNP-4 ACYCRIGACVSGERLTGACGLNGR 2313 (rat) IYRLCCR AP00223 Q62715,RatNP-2 VTCYCRSTRCGFRERLSGACGYRG 2314 (rat) RIYRLCCR AP00222 Q62716,RatNP-1 VTCYCRRTRCGFRERLSGACGYRG 2315 (rat) RIYRLCCR AP00174 Q64365,GNCP-1 RRCICTTRTCRFPYRRLGTCIFQNR 2316 (Guinea pig VYTFCC neutrophilcationic peptide 1) AP00311 Q90W78, Galensin CYSAAKYPGFQEFINRKYKSSRF2317 (frog) AP00395 Q95NT0, HSSGYTRPLPKPSRPIFIRPIGCDVC 2318 Penaeidin-4aYGIPSSTARLCCFRYGDCCHR (shrimp, Crustacea) AP00423 Q962B0,QGYKGPYTRPILRPYVRPVVSYNA 2319 Penaeidin-3n CTLSCRGITTTQARSCSTRLGRCCH(shrimp, Crustacea) VAKGYS AP00422 Q962B1, QGCKGPYTRPILRPYVRPVVSYNA 2320Penaeidin-3m CTLSCRGITTTQARSCCTRLGRCCH (shrimp, Crustacea) VAKGYSAP00421 Q963C3, YSSGYTRPLPKPSRPIFIRPIGCDVC 2321 Penaeidin-4CYGIPSSTARLCCFRYGDCCHR (shrimp, Crustacea) AP00210 Q99134, PGLaGMASKAGAIAGKIAKVALKAL 2322 (African clawed frog, XXA) AP00054 Q9DET7,GIGGALLSAGKSALKGLAKGLAEH 2323 Bombinin-like FAN peptide 7 (BLP-7, toad)AP00315 Q9PT75, SLGSFLKGVGTTLASVGKVVSDQF 2324 Dermatoxin (Two- GKLLQAGQcolored leaf frog) AP00133 Q9Y0Y0, Cecropin GGLKKLGKKLEGVGKRVFKASEK 2325B (insect, ALPVLTGYKAIG mosquito) AP00004 Ref, Ct-AMP1NLCERASLTWTGNCGNTGHCDTQ 2326 (CtAMP1, C. CRNWESAKHGACHKRGNWKCFCternatea- YFDC antimicrobial peptide 1, plant defensin) AP00027 Ref,hexapeptide RRWQWR 2327 (synthetic) AP00529 Ref, LantibioticWKSESVCTPGCVTGVLQTCFLQTI 2328 Ericin S (bacteria) TCNCHISK AP00306 Ref,Tigerinin-4 RVCYAIPLPIC 2329 (frog) AP00309 Ref, Human KS-27KSKEKIGKEFKRIVQRIKDFLRNLV 2330 (KS27 from LL-37) PR AP00344 Ref,Apidaecin II GNNRPIYIPQPRPPHPRL 2331 (honeybee, insect) AP00424 Ref, XT1(frog) GFLGPLLKLAAKGVAKVIPHLIPSR 2332 QQ AP00425 Ref, XT 2 (frog)GCWSTVLGGLKKFAKGGLEAIVNPK 2333 AP00426 Ref, XT 4 (frog)GVFLDALKKFAKGGMNAVLNPK 2334 AP00427 Ref, XT 7 (frog) GLLGPLLKIAAKVGSNLL2335 AP00431 Ref, human LLP 1 RVIEVVQGACRAIRHIPRRIRQGLE 2336 RIL AP00432Ref, human LLP RIAGYGLRGLAVIIRICIRGLNLIFEI 2337 IR AP00447 Ref, AnoplinGLLKRIKTLL 2338 (insect) AP00474 Ref, Piscidin 3 FIHHIFRGIVHAGRSIGRFLTG2339 (fish) AP00481 Ref, Kaliocin-1 FFSASCVPGADKGQFPNLCRLCAG 2340(synthetic) TGENKCA AP00482 Ref, Thionin KSCCRNTWARNCYNVCRLPGTISR 2341mutation EICAKKCRCKIISGTTCPSDYPK (synthetic) AP00484 Ref, StomoxynRGFRKHFNKLVKKVKHTISETAHV 2342 (insect, fly) AKDTAVIAGSGAAVVAAT AP00486Ref, Cupiennin 1b GFGSLFKFLAKKVAKTVAKQAAK 2343 (spider) QGAKYIANKQMEAP00487 Ref, Cupiennin 1c GFGSLFKFLAKKVAKTVAKQAAK 2344 (spider)QGAKYIANKQTE AP00488 Ref, Cupiennin 1D GFGSLFKFLAKKVAKTVAKQAAK 2345(spider) QGAKYVANKHME AP00489 Ref, Hipposin SGRGKTGGKARAKAKTRSSRAGL 2346(fish) QFPVGRVHRLLRKGNYAHRVGAG APVYL AP00923 Ref,AISYGNGVYCNKEKCWVNKAENK 2347 Carnobacteriocin QAITGIVIGGWASSLAGMGH B1(XXO, class IIa bacteriocin, bacteria) AP00496 Ref, HP 2-20AKKVFKRLEKLFSKIQNDK 2348 (synthetic) AP00497 Ref, Maximin H5ILGPVLGLVSDTLDDVLGIL 2349 (toad) AP00498 Ref, rCRAMP (ratGLVRKGGEKFGEKLRKIGQKIKEF 2350 cathelicidin) FQKLALEIEQ AP00500 Ref,S9-P18 KWKLFKKISKFLHLAKKF 2351 (synthetic) AP00501 Ref, L9-P18KWKLFKKILKFLHLAKKF 2352 (synthetic) AP00502 Ref, ClavaspirinFLRFIGSVIHGIGHLVHHIGVAL 2353 (sea squirt, tunicate) AP00503 Ref, humanP- AKRHHGYKRKFH 2354 113D AP00504 Ref, human MUC7 LAHQKPFIRKSYKCLHKRCR2355 20-Mer AP00507 Ref, Nigrocin 2 GLLSKVLGVGKKVLCGVSGLC 2356 (frog)AP00508 Ref, Nigrocin 1 GLLDSIKGMAISAGKGALQNLLKV 2357 (frog) ASCKLDKTCAP00509 Ref, human VAIALKAAHYHTHKE 2358 Calcitermin AP00510 Ref,Dicynthaurin ILQKAVLDCLKAAGSSLSKAAITAI 2359 (sea peach) YNKIT AP00511Ref, KIGAKI KIGAKIKIGAKIKIGAKI 2360 (synthetic) AP00516 Ref, Lycotoxin IIWLTALKFLGKHAAKHLAKQQLS 2361 (spider) KL AP00517 Ref, Lycotoxin IIKIKWFKTMKSIAKFIAKEQMKKHL 2362 (spider) GGE AP00518 Ref, Ib-AMP3QYRHRCCAWGPGRKYCKRWC 2363 (plant defensin, balsam) AP00519 Ref, Ib-AMP4EWGRRCCGWGPGRRYCRRWC 2364 (plant defensin, balsam) AP00521 Ref, Dhvar4KRLFKKLLFSLRKY 2365 (synthetic) AP00522 Ref, Dhvar5 LLLFLLKKRKKRKY 2366(synthetic) AP00525 Ref, Maximin H2 ILGPVLSMVGSALGGLIKKI 2367 (toad)AP00526 Ref, Maximin H3 ILGPVLGLVGNALGGLIKKI 2368 (toad) AP00527 Ref,Maximin H4 ILGPVISKIGGVLGGLLKNL 2369 (toad) AP00528 Ref, Anionic DDDDDD2370 peptide SAAP (sheep) AP00530 Ref, LantibioticVLSKSLCTPGCITGPLQTCYLCFPT 2371 Ericin A (bacteria) FAKC AP00531 Ref,Kenojeinin I GKQYFPKVGGRLSGKAPLAAKTH 2372 (sea skate) RRLKP AP00532 Ref,Lunatusin KTCENLADTFRGPCFATSNC 2373 (plant, ZZHp) AP00533 Ref, Fallaxin(frog) GVVDILKGAAKDIAGHLASKVMN 2374 KL AP00534 Ref, Tu-AMP 2KSCCRNTTARNCYNVCRIPG 2375 (TuAMP2, thionin- like antimicrobial peptides,plant defensin, tulip) AP00535 Ref, Pilosulin 1 GLGSVFGRLARILGRVIPKVAKKL2376 (Myr b I) GPKVAKVLPKVMKEAIPMAVEMA (Australian ants) KSQEEQQPQAP00536 Ref, Luxuriosin SVRTQDNAVNRQIFGSNGPYRDFQ 2377 (insect)LSDCYLPLETNPYCNEWQFAYHW NNALMDCERAIYHGCNRTRNNFIT LTACKNQAGPICNRRRHAP00537 Ref, SAMP H1 AEVAPAPAAAAPAKAPKKKAAAK 2378 (fish, AtlanticPKKAGPS salmon) AP00538 Ref, Halocidin WLNALLHHGLNCAKGVLA 2379 (dimerHal18 + Hal15) (tunicate) AP00539 Ref, AOD GFGCPWNRYQCHSHCRSIGRLGGY 2380(American oyster CAGSLRLTCTCYRS defensin, animal defensin) AP00540 Ref,Pentadactylin GLLDTLKGAAKNVVGSLASKVME 2381 (frog) KL AP00541 Ref,Polybia-MPI IDWKKLLDAAKQIL 2382 (insect, social wasp) AP00542 Ref,Polybia-CP ILGTILGLLKSL 2383 (insect, social wasp) AP00543 Ref,Ocellatin-1 GVVDILKGAGKDLLAHLVGKISEKV 2384 (XXA, frog) AP00544 Ref,Ocellatin-2 GVLDIFKDAAKQILAHAAEKQI 2385 (XXA, frog) AP00545 Ref,Ocellatin-3 GVLDILKNAAKNILAHAAEQI 2386 (frog) AP00548 Ref, CMAP 27RFGRFLRKIRRFRPKVTITIQGSARFG 2387 (chicken myeloid antimicrobial peptide27, bird cathelicidin, chicken cathelicidin) AP00550 Ref, Tu-AMP-1KSCCRNTVARNCYNVCRIPGTPRP 2388 (TuAMP1, thionin- VCAATCDCKLITGTKCPPGYEKlike antimicrobial peptides, plant defensin, tulip) AP00551 Ref, Combi-2FRWWHR 2389 (synthetic) AP00552 Ref, Maximin 9 GIGRKFLGGVKTTFRCGVKDFASK2390 (frog) HLY AP00554 Ref, Sl moricin GKIPVKAIKKAGAAIGKGLRAINIA 2391(insect) STAHDVYSFFKPKHKKK AP00555 Ref, Parasin I KGRGKQGGKVRAKAKTRSS2392 (catfish) AP00556 Ref, Kassinatuerin- GFMKYIGPLIPHAVKAISDLI 2393 1(frog) AP00557 Ref, Fowlicidin-1 RVKRVWPLVIRTVIAGYNLYRAIK 2394(chCATH-1, bird KK cathelicidin, chicken cathelicidin) AP00559 Ref,Eryngin ATRVVYCNRRSGSVVGGDDTVYY 2395 (mushroom, fungi) EG AP00560 Ref,Dendrocin TTLTLHNLCPYPVWWLVTPNNGG 2396 (plant, bamboo) FPIIDNTPVVLGAP00561 Ref, Coconut EQCREEEDDR 2397 antifungal peptide (plant) AP00562Ref, Pandinin 1 GKVWDWIKSAAKKIWSSEPVSQL 2398 (African scorpion)KGQVLNAAKNYVAEKIGATPT AP00563 Ref, White cloud KTCENLADTFRGPCFATSNCDDHC2399 bean defensin KNKEHLLSGRCRDDFRCWCTRNC (plant defensin) AP00564 Ref,Dybowskin-1 FLIGMTHGLICLISRKC 2400 (frog) AP00565 Ref, Dybowskin-2FLIGMTQGLICLITRKC 2401 (frog) AP00566 Ref, Dybowskin-3GLFDVVKGVLKGVGKNVAGSLLE 2402 (frog) QLKCKLSGGC AP00567 Ref, Dybowskin-4VWPLGLVICKALKIC 2403 (frog) AP00568 Ref, Dybowskin-5GLFSVVTGVLKAVGKNVAKNVGG 2404 (frog) SLLEQLKCKKISGGC AP00569 Ref,Dybowskin-6 FLPLLLAGLPLKLCFLFKKC 2405 (frog) AP00570 Ref, Pleurain-A1SIITMTKEAKLPQLWKQIACRLYNTC 2406 (frog) AP00571 Ref, Pleurain-A2SIITMTKEAKLPQSWKQIACRLYNTC 2407 (frog) AP00574 Ref, Esculentin-GLFSKFAGKGIKNLIFKGVKHIGKE 2408 IGRa (frog) VGMDVIRTGIDVAGCKIKGEC AP00575Ref, Brevinin- GLLDTFKNLALNAAKSAGVSVLNS 2409 2GRa (frog) LSCKLSKTCAP00576 Ref, Brevinin- GVLGTVKNLLIGAGKSAAQSVLKT 2410 2GRb (frog)LSCKLSNDC AP00577 Ref, Brevinin- GLFTLIKGAAKLIGKTVAKEAGKT 2411 2GRc(frog) GLELMACKITNQC AP00578 Ref, Brevinin- FLPLLAGLAANFLPKIFCKITKKC2412 1GRa (frog) AP00579 Ref, Nigrocin- GLLSGILGAGKHIVCGLSGLC 2413 2GRa(frog) AP00580 Ref, Nigrocin- GLFGKILGVGKKVLCGLSGMC 2414 2GRb (frog)AP00581 Ref, Nigrocin- GLLSGILGAGKNIVCGLSGLC 2415 2GRc (frog) AP00582Ref, Brevinin- GFSSLFKAGAKYLLKSVGKAGAQ 2416 2GHa (frog) QLACKAANNCAAP00583 Ref, Brevinin- GVITDALKGAAKTVAAELLRKAH 2417 2GHb (frog) CKLTNSCAP00584 Ref, Guentherin VIDDLKKVAKKVRRELLCKKHHK 2418 (frog) KLN AP00585Ref, Brevinin- SIWEGIKNAGKGFLVSILDKVRCK 2419 2GHc (frog) VAGGCNP AP00586Ref, Temporin-GH FLPLLFGAISHLL 2420 (frog) AP00587 Ref, Brevinin-2TSaGIMSLFKGVLKTAGKHVAGSLVD 2421 (frog) QLKCKITGGC AP00588 Ref,Brevinin-1TSa FLGSIVGALASALPSLISKIRN 2422 (frog) AP00589 Ref, Temporin-FLGALAKIISGIF 2423 1TSa (frog) AP00593 Ref, Brevinin-1CSaFLPILAGLAAKIVPKLFCLATKKC 2424 (frog) AP00594 Ref, Temporin-FLPIVGKLLSGLL 2425 1CSa (frog) AP00595 Ref, Temporin- FLPIIGKLLSGLL 24261CSb (frog) AP00596 Ref, Temporin- FLPLVTGLLSGLL 2427 1CSc (frog)AP00597 Ref, Temporin- NFLGTLVNLAKKIL 2428 1CSd (frog) AP00598 Ref,Temporin- FLSAITSLLGKLL 2429 1SPb (frog) AP00599 Ref, Brevinin-2-GIWDTIKSMGKVFAGKILQNL 2430 related (frog) AP00600 Ref, Odorranain-GLLRASSVWGRKYYVDLAGCAKA 2431 HP (frog) AP00601 Ref, Brevinin-FLSLALAALPKFLCLVFKKC 2432 1DYa (frog) AP00602 Ref, Brevinin-FLSLALAALPKLFCLIFKKC 2433 1DYb (frog) AP00603 Ref, Brevinin-FLPLLLAGLPKLLCLFFKKC 2434 1DYc (frog) AP00607 Ref, Brevinin-GLFDVVKGVLKGAGKNVAGSLLE 2435 2DYb (frog) QLKCKLSGGC AP00608 Ref,Brevinin- GLFDVVKGVLKGVGKNVAGSLLE 2436 2DYc (frog) QLKCKLSGGC AP00609Ref, Brevinin- GIFDVVKGVLKGVGKNVAGSLLE 2437 2DYd (frog) QLKCKLSGGCAP00610 Ref, Brevinin- GLFSVVTGVLKAVGKNVAKNVGG 2438 2DYe (frog)SLLEQLKCKISGGC AP00611 Ref, Temporin- FIGPIISALASLFG 2439 1DYa (frog)AP00615 Ref, Palustrin-1b ALFSILRGLKKLGNMGQAFVNCKI 2440 (frog) YKKCAP00616 Ref, Palustrin-1c ALSILRGLEKLAKMGIALTNCKAT 2441 (frog) KKCAP00617 Ref, Palustrin-1d ALSILKGLEKLAKMGIALTNCKAT 2442 (frog) KKCAP00619 Ref, Palustrin-2b GFFSTVKNLATNVAGTVIDTLKCK 2443 (frog) VTGGCRSAP00620 Ref, Palustrin-2c GFLSTVKNLATNVAGTVIDTLKCK 2444 (frog) VTGGCRSAP00621 Ref, Palustrin-3a GIFPKIIGKGIKTGIVNGIKSLVKGV 2445 (frog)GMKVFKAGLNNIGNTGCNEDEC AP00622 Ref, Palustrin-3bGIFPKIIGKGIKTGIVNGIKSLVKGV 2446 (frog) GMKVFKAGLSNIGNTGCNEDEC AP00624Ref, human ALL- ALLGDFFRKSKEKIGKEFKRIVQRI 2447 38 (an LL-37KDFLRNLVPRTES analog released from its precursor hCAP-18 by gastricsinin vivo) AP00625 Ref, human KR-20 KRIVQRIKDFLRNLVPRTES 2448 (KR20 fromLL- 37) AP00626 Ref, human KS-30 KSKEKIGKEFKRIVQRIKDFLRNLV 2449 (KS30from LL-37) PRTES AP00627 Ref, human RK-31 RKSKEKIGKEFKRIVQRIKDFLRNL2450 (RK31 from LL- VPRTES 37) AP00628 Ref, human LL-23LLGDFFRKSKEKIGKEFKRIVQR 2451 (LL23 from LL-37) AP00629 Ref, human LL-29LLGDFFRKSKEKIGKEFKRIVQRIK 2452 (LL29 from LL-37) DFLR AP00630 Ref,Amoeba GEILCNLCTGLINTLENLLTTKGAD 2453 peptide (protozoan para AP00631Ref, Mundticin KYYGNGVSCNKKGCSVDWGKAIG 2454 (bacteria)IIGNNSAANLATGGAAGWSK AP00638 Ref, Citropin 2.1 GLIGSIGKALGGLLVDVLKPKL2455 (frog) AP00639 Ref, Citropin 2.1.3 GLIGSIGKALGGLLVDVLKPKLQA 2456(frog) AS AP00640 Ref, Maculatin 1.3 GLLGLLGSVVSHVVPAIVGHF 2457 (frog)AP00641 Ref, Pardaxin 1 GFFALIPKIISSPLFKTLLSAVGSALS 2458 (Pardaxin P-1,SSGEQE Pardaxin P1, Pa1, flat fish) AP00642 Ref, Pardaxin 2GFFALIPKIISSPIFKTLLSAVGSALS 2459 (Pardaxin P-2, SSGGQE Pardaxin P2, Pa2,flat fish) AP00643 Ref, Pardaxin 3 GFFAFIPKIISSPLFKTLLSAVGSALS 2460(Pardaxin P-3, SSGEQE Pardaxin P3, Pa3, flat fish) AP00645 Ref, Pardaxin5 GFFAFIPKIISSPLFKTLLSAVGSALS 2461 (Pardaxin P-5, SSGDQE Pardaxin P5,Pa5, flat fish) AP00647 Ref, Brevinin-1PLb FLPLIAGLAANFLPKIFCAITKKC 2462(frog) AP00648 Ref, Brevinin-1PLc FLPVIAGVAAKFLPKIFCAITKKC 2463 (frog)AP00649 Ref, Esculentin- GLFPKINKKKAKTGVFNIIKTVGKE 2464 1PLa (frog)AGMDLIRTGIDTIGCKIKGEC AP00650 Ref, Esculentin-GIFTKINKKKAKTGVFNIIKTIGKEA 2465 1PLb (frog) GMDVIRAGIDTISCKIKGEC AP00651Ref, Esculentin- GLFSILKGVGKIALKGLAKNMGK 2466 2PLa (frog) MGLDLVSCKISKECAP00652 Ref, Ranatuerin- GIMDTVKNVAKNLAGQLLDKLKC 2467 2PLa (frog) KITACAP00653 Ref, Ranatuerin- GIMDTVKNAAKDLAGQLLDKLKC 2468 2PLb (frog) RITGCAP00654 Ref, Ranatuerin- GLLDTIKNTAKNLAVGLLDKIKCK 2469 2PLc (frog) MTGCAP00655 Ref, Ranatuerin- GIMDSVKNVAKNIAGQLLDKLKC 2470 2PLd (frog) KITGCAP00656 Ref, Ranatuerin- GIMDSVKNAAKNLAGQLLDTIKCK 2471 2PLe (frog) ITACAP00657 Ref, Ranatuerin- GIMDTVKNAAKDLAGQLDKLKCR 2472 2PLf (frog) ITGCAP00658 Ref, Temporin- FLPLVGKILSGLI 2473 1PLa (frog) AP00659 Ref,Ranatuerin 5 FLPIASLLGKYL 2474 (frog) AP00661 Ref, Esculentin-2LGILSLFTGGIKALGKTLFKMAGKA 2475 (frog) GAEHLACKATNQC AP00662 Ref,Esculentin-2B GLFSILRGAAKFASKGLGKDLTKL 2476 (ESC2B-RANBE, GVDLVACKISKQCfrog) AP00663 Ref, Esculentin-2P GFSSIFRGVAKFASKGLGKDLARL 2477 (frog)GVNLVACKISKQC AP00664 Ref, Peptide A1 FLPAIAGILSQLF 2478 (frog) AP00665Ref, Peptide B9 FLPLIAGLIGKLF 2479 (frog) AP00666 Ref, PG-L ( frog)EGGGPQWAVGHFM 2480 AP00667 Ref, PG-KI (frog) EPHPDEFVGLM 2481 AP00668Ref, PG-KII (frog) EPNPDEFVGLM 2482 AP00669 Ref, PG-KIII (frog)EPHPNEFVGLM 2483 AP00670 Ref, PG-SPI (frog) EPNPDEFFGLM 2484 AP00660Ref, Pandinin 2 FWGALAKGALKLIPSLFSSFSKKD 2485 (African scorpion) AP00671Ref, PG-SPII (frog) EPNPNEFFGLM 2486 AP00673 Ref, LantibioticWKSESVCTPGCVTGVLQTCFLQTI 2487 Ericin S (bacteria TCNCHISK AP00674 Ref,Lantibiotic VLSKSLCTPGCITGPLQTCYLCFPT 2488 Ericin A (bacteria FAKCAP00675 Ref, Human beta FELDRICGYGTARCRKKCRSQEYRI 2489 defensin 4(HBD-4, GRCPNTYACCLRKWDESLLNRTKP HBD4, human defensin) AP00676 Ref,RL-37 (RL37, RLGNFFRKVKEKIGGGLKKVGQKI 2490 monkey KDFLGNLVPRTAScathelicidin) AP00677 Ref, CAP11 GLRKKFRKTRKRIQKLGRKIGKTG 2491 (Guineapig RKVWKAWREYGQIPYPCRI cathelicidin) AP00678 Ref, CanineRLKELITTGGQKIGEKIRRIGQRIKD 2492 cathelicidin FFKNLQPREEKS (K9CATH) (dog)AP00679 Ref, Esculentin GLFSILKGVGKIAIKGLGKNLGKM 2493 2VEb (frog)GLDLVSCKISKEC AP00680 Ref, SMAP-34 GLFGRLRDSLQRGGQKILEKAERI 2494 (sheepcathelicidin) WCKIKDIFR AP00681 Ref, OaBac5 RFRPPIRRPPIRPPFRPPFRPPVRPPIR2495 (sheep cathelicidin) PPFRPPFRPPIGPFP AP00682 Ref, OaBac6RRLRPRHQHFPSERPWPKPLPLPLP 2496 (sheep cathelicidin)RPGPRPWPKPLPLPLPRPGLRPWPK PL AP00683 Ref, OaBac7.5RRLRPRRPRLPRPRPRPRPRPRSLPL 2497 (sheep cathelicidin)PRPQPRRIPRPILLPWRPPRPIPRPQI QPIPRWL AP00684 Ref, OaBac11RRLRPRRPRLPRPRPRPRPRPRSLPL 2498 (sheep cathelicidin)PRPKPRPIPRPLPLPRPRPKPIPRPLP LPRPRPRRIPRPLPLPRPRPRPIPRPL PLPQPQPSPIPRPLAP00685 Ref, Ranatuerin GIMDTVKGVAKTVAASLLDKLKC 2499 2VEb (frog) KITGCAP00686 Ref, eCATH-1 KRFGRLAKSFLRMRILLPRRKILLAS 2500 (horsecathelicidin) AP00687 Ref, eCATH-2 KRRHWFPLSFQEFLEQLRRFRDQL 2501 (horsecathelicidin) PFP AP00688 Ref, eCATH-3 KRFHSVGSLIQRHQQMIRDKSEAT 2502(horse cathelicidin) RHGIRIITRPKLLLAS AP00689 Ref, Prophenin-1AFPPPNVPGPRFPPPNFPGPRFPPPN 2503 (pig cathelicidin)FPGPRFPPPNFPGPRFPPPNFPGPPFP PPIFPGPWFPPPPPFRPPPFGPPRFP AP00690 Ref,Prophenin-2 AFPPPNVPGPRFPPPNVPGPRFPPPN 2504 (pig cathelicidin)FPGPRFPPPNFPGPRFPPPNFPGPPFP PPIFPGPWFPPPPPFRPPPFGPPRFP AP00691 Ref,HFIAP-1 GFFKKAWRKVKHAGRRVLDTAK 2505 (hagfish GVGRHYVNNWLNRYRcathelicidin) AP00692 Ref, HFIAP-3 GWFKKAWRKVKNAGRRVLKGVG 2506 (hagfishIHYGVGLI cathelicidin) AP00693 Ref, Trout cath RICSRDKNCVSRPGVGSIIGRPGGG2507 (fish cathelicidin) SLIGRPGGGSVIGRPGGGSPPGGGS FNDEFIRDHSDGNRFAAP00694 Ref, MRP AIGSILGALAKGLPTLISWIKNR 2508 (melittin-related peptide)AP00695 Ref, Temporin- FLPILGKLLSGIL 2509 1TGa (frog) AP00696 Ref,Dahlein 1.1 GLFDIIKNIVSTL 2510 (frog) AP00697 Ref, Dahlein 1.2GLFDIIKNIFSGL 2511 (frog) AP00698 Ref, Dahlein 4.1GLWQLIKDKIKDAATGFVTGIQS 2512 (frog) AP00699 Ref, Dahlein 4.2GLWQFIKDKLKDAATGLVTGIQS 2513 (frog) AP00700 Ref, Dahlein 4.3GLWQFIKDKFKDAATGLVTGIQS 2514 (frog) AP00701 Ref, Dahlein 5.1GLLGSIGNAIGAFIANKLKP 2515 (frog) AP00702 Ref, Dahlein 5.2GLLGSIGNAIGAFIANKLKPK 2516 (frog) AP00703 Ref, Dahlein 5.3GLLASLGKVLGGYLAEKLKP 2517 (frog) AP00704 Ref, Dahlein 5.4GLLGSIGKVLGGYLAEKLKPK 2518 (frog) AP00705 Ref, Dahlein 5.5GLLASLGKVLGGYLAEKLKPK 2519 (frog) AP00706 Ref, Dahlein 5.6GLLASLGKVFGGYLAEKLKPK 2520 (frog) AP00709 Ref, MytilusGFGCPNDYPCHRHCKSIPGRAGGY 2521 defensin (mytilin) CGGAHRLRCTCYR A(mollusc) AP00711 Ref, Mussel GFGCPNNYACHQHCKSIRGYCGG 2522 defensin MGD2YCAGWFRLRCTCYRCG AP00712 Ref, scorpion GFGCPLNQGACHRHCRSIRRRGGY 2523defensin CAGFFKQTCCYRN AP00713 Ref, Androctonus GFGCPFNQGACHRHCRSIRRRGGY2524 defensin CAGLFKQTCTCYR AP00714 Ref, OrinthodorosGYGCPFNQYQCHSHCSGIRGYKGG 2525 defensin A (soft YCKGTFKQTCKCY ticks)AP00715 Ref, VaD1 (plant RTCMKKEGWGKCLIDTTCAHSCK 2526 defensin)NRGYIGGNCKGMTRTCYCLVNC AP00722 Ref, Cryptonin GLLNGLALRLGKRALKKIIKRLCR2527 (insect, cicada) AP00723 Ref, Decoralin SLLSLLRKLIT 2528 (insect)AP00724 Ref, RTD-2 (rhesus RCLCRRGVCRCLCRRGVC 2529 theta-defensin-2,minidefensin, XXC, BBS, lectin, ZZHa) AP00725 Ref, RTD-3 (rhesusRCICTRGFCRCICTRGFC 2530 theta-defensin-3, minidefensin, XXC, BBS,lectin, ZZHa) AP00726 Ref, Combi-1 RRWWRF 2531 (synthetic) AP00748 Ref,Gm pro-rich DIQIPGIKKPTHRDIIIPNWNPNVRT 2532 pept1 (insect) QPWQRFGGNKSAP00749 Ref, Gm anionic EADEPLWLYKGDNIERAPTTADHP 2533 pept 1 (insect)ILPSIIDDVKLDPNRRYA AP00750 Ref, Gm pro-rich EIRLPEPFRFPSPTVPKPIDIDPILPHP2534 pept 2 (insect) WSPRQTYPIIARRS AP00752 Ref, Gm defensin-DKLIGSCVWGATNYTSDCNAECK 2535 like peptide (insect) RRGYKGGHCGSFWNVNCWCEEAP00753 Ref, Gm VQETQKLAKTVGANLEETNKKLA 2536 apolipophoricinPQIKSAYDDFVKQAQEVQKKLHE (insect) AASKQ AP00754 Ref, Gm anionicETESTPDYLKNIQQQLEEYTKNFNT 2537 pept2 (insect) QVQNAFDSDKIKSEVNNFIESLGKILNTEKKEAPK AP00755 Ref, Gm cecropin ENFFKEIERAGQRIRDAIISAAPAVE 2538D-like pept, insect TLAQAQKIIKGGD AP00756 Ref, Dermaseptin-ALWKDILKNAGKAALNEINQLVNQ 2539 B6 (DRS-B6, DRS B6, XXA, frog) AP00759Ref, Phylloseptin- FLSLIPHAINAVSTLVHHSG 2540 O1 (PLS-O1, Phylloseptin-4,PS- 4, XXA, frog) AP00760 Ref, Phylloseptin- FLSLIPHAINAVSAIAKHS 2541 O2(PLS-O2, Phylloseptin-5, PS- 5, XXA, frog) AP00761 Ref, Phylloseptin-6SLIPHAINAVSAIAKHF 2542 (Phylloseptin-H4, PLS-H4, PS-6, XXA, frog)AP00762 Ref, Phylloseptin-7 FLSLIPHAINAVSAIAKHF 2543 (Phylloseptin-H5,PLS-H5, PS-7, XXA, frog) AP00763 Ref, DermaseptinGLWSTIKNVGKEAAIAAGKAALG 2544 DPh-1 (XXA, frog) AL AP00764 Ref,Dermaseptin- GLRSKIWLWVLLMIWQESNKFKKM 2545 S9 (DRS-S9, DRS S9, frog)AP00765 Ref, Human salvic MHDFWVLWVLLEYIYNSACSVLS 2546ATSSVSSRVLNRSLQVKVVKITN AP00766 Ref, Gassericin AIYWIADQFGIHLATGTARKLLDAM 2547 (XXC, XXD2, ASGASLGTAFAAILGVTLPAWALA classIV AAGALGATAA bacteriocin, Gram- positive bacteria) AP00767 Ref,Circularin A VAGALGVQTAAATTIVNVILNAGT 2548 (XXC, class IVLVTVLGIIASIASGGAGTLMTIGWA bacteriocin, Gram- TFKATVQKLAKQSMARAIAYpositive bacteria) AP00768 Ref, Closticin 574 PNWTKIGKCAGSIAWAIGSGLFGG2549 (bacteria) AKLIKIKKYIAELGGLQKAAKLLV GATTWEEKLHAGGYALINLAAELTGVAGIQANCF AP00769 Ref, Caerin 1.11 GLLGAMFKVASKVLPHVVPAITEHF 2550 (XXA,frog) AP00770 Ref, Maculatin 1.4 GLLGLLGSVVSHVLPAITQHL 2551 (XXA, frog)AP00771 Ref, Magainin 1 GIGKFLHSAGKFGKAFVGEIMKS 2552 (frog) AP00772 Ref,Oxyopinin 1 FRGLAKLLKIGLKSFARVLKKVLP 2553 (spider)KAAKAGKALAKSMADENAIRQQNQ AP00773 Ref, Oxyopinin 2aGKFSVFGKILRSIAKVFKGVGKVR 2554 (spider) KQFKTASDLDKNQ AP00774 Ref,Oxyopinin 2b GKFSGFAKILKSIAKFFKGVGKVR 2555 (spider) KGFKEASDLDKNQAP00775 Ref, Oxyopinin 2c GKLSGISKVLRAIAKFFKGVGKAR 2556 (spider)KQFKEASDLDKNQ AP00776 Ref, Oxyopinin 2d GKFSVFSKILRSIAKVFKGVGKVRK 2557(spider) GFKTASDLDKNQ AP00777 Ref, NRC-1 (XXA, GKGRWLERIGKAGGIIIGGALDHL2558 fish, gene predicted) AP00778 Ref, NRC-2 (XXA, WLRRIGKGVKIIGGAALDHL2559 fish, gene predicted) AP00779 Ref, NRC-3 (XXA,GRRKRKWLRRIGKGVKIIGGAALD 2560 fish, gene HL predicted) AP00781 Ref,NRC-5 (XXA, FLGALIKGAIHGGRFIHGMIQNHH 2561 fish, gene predicted) AP00782Ref, NRC-6 (XXA, GWGSIFKHGRHAAKHIGHAAVNH 2562 fish, gene YL predicted)AP00783 Ref, NRC-7 (XXA, RWGKWFKKATHVGKHVGKAALT 2563 fish, gene AYLpredicted) AP00784 Ref, NRC-10 FFRLLFHGVHHVGKIKPRA 2564 (XXA, fish, genepredicted) AP00785 Ref, NRC-11 GWKSVFRKAKKVGKTVGGLALD 2565 (XXA, fish,gene HYL predicted) AP00786 Ref, NRC-12 GWKKWFNRAKKVGKTVGGLAVD 2566(XXA, fish, gene HYL predicted) AP00787 Ref, NRC-13GWRLLLKKAEVKTVGKLALKHYL 2567 (XXA, fish, gene predicted) AP00788 Ref,NRC-14 AGWGSIFKHIFKAGKFIHGAIQAHND 2568 (XXA, fish, gene predicted)AP00789 Ref, NRC-15 GFWGKLFKLGLHGIGLLHLHL 2569 (XXA, fish, genepredicted) AP00790 Ref, NRC-16 GWKKWLRKGAKHLGQAAIK 2570 (XXA, fish, genepredicted) AP00791 Ref, NRC-17 GWKKWLRKGAKHLGQAAIKGLAS 2571 (XXA, fish,gene predicted) AP00792 Ref, NRC-19 FLGLLFHGVHHVGKWIHGLIHGHH 2572 (XXA,fish, gene predicted) AP00793 Ref, Bombinin H2 IIGPVLGLVGSALGGLLKKI 2573(XXA, frog) AP00794 Ref, Bombinin H3 IIGPVLGMVGSALGGLLKKI 2574 (frog,XXD, XXA) AP00795 Ref, Bombinin H7 ILGPILGLVSNALGGLL 2575 (frog, XXD,XXA) AP00796 Ref, Bombinin GH- IIGPVLGLVGKPLESLLE 2576 1L (XXA, toad)AP00797 Ref, Bombinin GH- IIGPVLGLVGKPLESLLE 2577 1D (toad, XXD, XXA)AP00807 Ref, Enterocin E- NRWYCNSAAGGVGGAAGCVLAG 2578 760 (bacteriocin,YVGEAKENIAGEVRKGWGMAGGF bacteria) THNKACKSFPGSGWASG AP00808 Ref,hepcidin (fish) CRFCCRCCPRMRGCGLCCRF 2579 AP00809 Ref, hepcidin TH1-GIKCRFCCGCCTPGICGVCCRF 2580 5 (fish) AP00810 Ref, hepcidin TH2-QSHLSLCRWCCNCCRSNKGC 2581 3 (fish) AP00811 Ref, human LEAP-2MTPFWRGVSLRPIGASCRDDSECIT 2582 RLCRKRRCSLSVAQE AP00812 Ref, EnkelytinFAEPLPSEEEGESYSKEPPEMEKRY 2583 (cow) GGFM AP00732 Ref, Spheniscin-1SFGLCRLRRGSCAHGRCRFPSIPIG 2584 (Sphe-1, avian RCSRFVQCCRRVW defensin)AP00733 Ref, Organgutan LLGDFFRKAREKIGEEFKRIVQRIK 2585 ppyLL-37 (GreatDFLRNLVPRTES Ape, primate cathelicidin) AP00734 Ref, GibbonSLGNFFRKARKKIGEEFKRIVQRIK 2586 hmdSL-37 DFLQHLIPRTEA (hylobatidae,primate cathelicidin) AP00735 Ref, pobRL-37 RLGNFFRKAKKKIGRGLKKIGQKI2587 (cercopithecidae, KDFLGNLVPRTES primate cathelicidin) AP00736 Ref,cjaRL-37 RLGDILQKAREKIEGGLKKLVQKI 2588 (primate KDFFGKFAPRTEScathelicidin) AP00737 Ref, Plasticin GLVTSLIKGAGKLLGGLFGSVTG 2589 PBN2KF(XXA, DRP-PBN2, frog) AP00738 Ref, Plasticin GLVTGLLKTAGKLLGDLFGSLTG2590 ANCKF (XXA, synthetic) AP00739 Ref, PlasticinGVVTDLLKTAGKLLGNLFGSLSG 2591 PD36KF (XXA, synthetic) AP00740 Ref,Plasticin GVVTDLLKTAGKLLGNLVGSLSG 2592 PD36K (XXA, synthetic) AP00741Ref, Chicken PITYLDAILAAVRLLNQRISGPCILR 2593 cathelicidin-B1LREAQPRPGWVGTLQRRREVSFLV (bird cathelicidin) EDGPCPPGVDCRSCEPGALQHCVGTVSIEQQPTAELRCRPLRPQ AP00742 Ref, Chicken MRILYLLLSVLFVVLQGVAGQPYF 2594gallinacin 4 (Gal 4) SSPIHACRYQRGVCIPGPCRWPYY RVGSCGSGLKSCCVRNRWAAP00743 Ref, Chicken MKILCFFIVLFVAVHGAVGFSRSPR 2595 gallinacin 7 (Gal 7)YHMQCGYRGTFCTPGKCPYGNAY LGLCRPKYSCCRWL AP00744 Ref, ChickenMQILPLLFAVLLLMLRAEPGLSLA 2596 gallinacin 9 (Gal 9)RGLPQDCERRGGFCSHKSCPPGIGR IGLCSKEDFCCRSRWYS AP00745 Ref, ChickenMTPFWRGVSLRPVGASCRDNSECI 2597 LEAP-2 (cLEAP- TMLCRKNRCFLRTASE 2) AP00814Ref, Caerulein GLGSILGKILNVAGKVGKTIGKVA 2598 precursor-related DAVGNKEfragment Ea (CPRF-Ea, frog) AP00815 Ref, CaeruleinGLGSFLKNAIKIAGKVGSTIGKVAD 2599 precursor-related AIGNKE fragment Eb(CPRF-Eb, frog) AP00816 Ref, Caerulein GLGSFFKNAIKIAGKVGSTIGKVAD 2600precursor-related AIGNKE fragment Ec (CPRF-Ec, frog) AP00817 Ref,Temporin-1Oa FLPLLASLFSRLL 2601 (frog) AP00818 Ref, Temporin-1ObFLPLIGKILGTIL 2602 (frog) AP00819 Ref, Temporin-1Oc FLPLLASLFSRLF 2603(frog) AP00820 Ref, Temporin-1Od FLPLLASLFSGLF 2604 (frog) AP00821 Ref,Brevinin-20a GLFNVFKGLKTAGKHVAGSLLNQ 2605 (frog) LKCKVSGGC AP00822 Ref,Brevinin-20b GIFNVFKGALKTAGKHVAGSLLNQ 2606 (frog) LKCKVSGEC AP00824 Ref,Temporin-1Gb SILPTIVSFLSKFL 2607 (XXA, frog) AP00825 Ref, Temporin-1GcSILPTIVSFLTKFL 2608 (XXA, frog) AP00826 Ref, Temporin-1Gd FILPLIASFLSKFL2609 (XXA, frog) AP00827 Ref, Ranatuerin- SMISVLKNLGKVGLGFVACKVNK 26101Ga (frog) QC AP00829 Ref, Ranalexin-1G FLGGLMKIIPAAFCAVTKKC 2611 (frog)AP00830 Ref, Ranatuerin-2G GLLLDTLKGAAKDIAGIALEKLKC 2612 (frog) KITGCKPAP00831 Ref, Odorranain- GLLSGILGAGKHIVCGLTGCAKA 2613 NR (frog) AP00832Ref, Maximin H1 ILGPVISTIGGVLGGLLKNL 2614 (XXA, toad) AP00834 Ref, G.mellonella KVNANAIKKGGKAIGKGFKVISAA 2615 moricin-like STAHDVYEHIKNRRHpeptide A (Gm- mlpA, insect) AP00835 Ref, G. mellonellaGKIPVKAIKKGGQIIGKALRGINIAS 2616 moricin-like TAHDIISQFKPKKKKNH peptide B(Gm- mlpB, insect) AP00836 Ref, G. mellonella KVPIGAIKKGGKIIKKGLGVIGAAG2617 moricin-like TAHEVYSHVKNRH peptide C1 (Gm- mlpC1, insect) AP00837Ref, G. mellonella KVPIGAIKKGGKIIKKGLGVLGAA 2618 moricin-likeGTAHEVYNHVRNRQ peptide C2 (Gm- mlpC2, insect) AP00838 Ref, G. mellonellaKVPIGAIKKGGKIIKKGLGVIGAAG 2619 moricin-like TAHEVYSHVKNRQ peptide C3(Gm- mlpC3, insect) AP00839 Ref, G. mellonella KVPVGAIKKGGKAIKTGLGVVGA2620 moricin-like AGTAHEVYSHIRNRH peptide C4/C5 (Gm-mlpC4/C5, insect)AP00840 Ref, G. mellonella KGIGSALKKGGKIIKGGLGALGAIG 2621 moricin-likeTGQQVYEHVQNRQ peptide D (Gm- mlpD, insect) AP00841 Ref, Enterocin ATTHSGKYYGNGVYCTKNKCTVD 2622 (EntA, class IIA WAKATTCIAGMSIGGFLGGAIPGKCbacteriocin, i.e. pediocin-like peptide, bacteria) AP00842 Ref, DivercinV41 TKYYGNGVYCNSKKCWVDWGQA 2623 (DvnV41, class IIa SGCIGQTVVGGWLGGAIPGKCbacteriocin, pediocin-like peptide, bacteria. DvnRV41 is the recombinantform) AP00843 Ref, Divergicin TKYYGNGVYCNSKKCWVDWGTA 2624 M35 (class IIaQGCIDVVIGQLGGGIPGKGKC bacteriocin, pediocin-like peptide, bacteria)AP00844 Ref, Coagulin KYYGNGVTCGKHSCSVDWGKATT 2625 (bacteriocin,CIINNGAMAWATGGHQGTHKC pediocin-like peptide, bacteria) AP00845 Ref,Listeriocin KSYGNGVHCNKKKCWVDWGSAIS 2626 743A (class IIaTIGNNSAANWATGGAAGWKS bacteriocin, pediocin-like peptide, bacteria)AP00846 Ref, Mundticin KS KYYGNGVSCNKKGCSVDWGKAIG 2627 (enterocin CRL35,IIGNNSAANLATGGAAGWKS mundticin ATO6, mundticin QU2, class IIabacteriocin, pediocin-like peptide, bacteria) AP00847 Ref, Sakacin 5XKYYGNGLSCNKSGCSVDWSKAISII 2628 (Sak5X, class IIa GNNAVANLTTGGAAGWKSbacteriocin, pediocin-like peptide, bacteria) AP00848 Ref, Leucocin CKNYGNGVHCTKKGCSVDWGYAW 2629 (class IIa ANIANNSVMNGLTGGNAGWHNbacteriocin, pediocin-like peptide, bacteria) AP00849 Ref, LactococcinTSYGNGVHCNKSKCWIDVSELETY 2630 MMFII (class IIa KAGTVSNPKDILWbacteriocin, pediocin-like peptide, bacteria) AP00850 Ref, Sakacin GKYYGNGVSCNSHGCSVNWGQAW 2631 (SakG, class IIa TCGVNHLANGGHGVCbacteriocin, pediocin-like peptide, bacteria) AP00851 Ref, PlantaricinKYYGNGVTCGKHSCSVNWGQAFS 2632 423 (class IIa CSVSHLANFGHGKC bacteriocin,pediocin-like peptide, bacteria) AP00852 Ref, PlantaricinKYYGNGLSCSKKGCTVNWGQAFS 2633 C19 (class IIa CGVNRVATAGHHKC bacteriocin,pediocin-like peptide, bacteria) AP00853 Ref, Enterocin PATRSYGNGVYCNNSKCWVNWGE 2634 (EntP, class IIa AKENIAGIVISGWASGLAGMGHbacteriocin, pediocin-like peptide, bacteria) AP00854 Ref, Bacteriocin31 ATYYGNGLYCNKQKCWVDWNKA 2635 (Bac 31, Bac31, SREIGKIIVNGWVQHGPWAPRclass IIa bacteriocin, pediocin-like peptide, bacteria) AP00855 Ref,MSI-78 GIGKFLKKAKKFGKAFVKILKK 2636 (XXA, synthetic) AP00856 Ref, MSI-594GIGKFLKKAKKGIGAVLKVLTTGL 2637 (XXA, synthetic) AP00857 Ref, CatestatinSSMKLSFRARAYGFRGPGPQL 2638 (human CHGA(352-372), human Cst) AP00858 Ref,Temporin D LLPIVGNLLNSLL 2639 (XXA, frog) AP00859 Ref, Temporin HLSPNLLKSLL 2640 (XXA, frog) AP00861 Ref, Brevinin-ALbFLPLAVSLAANFLPKLFCKITKKC 2641 (frog) AP00862 Ref, Brevinin 1EFLPLLAGLAANFLPKIFCKITKRC 2642 (frog) AP00863 Ref, Temporin-FLPIVGKLLSGLSGLL 2643 ALa (XXA, frog) AP00864 Ref, TemporinFLPIVGRLISGLL 2644 1ARa (XXA, frog) AP00865 Ref, Temporin FLPIIGQLLSGLL2645 1AUa (XXA, Temporin-1AUa) (frog) AP00866 Ref, TemporinFLPIIAKVLSGLL 2646 1Bya (XXA, Temporin-1Bya, frog) AP00867 Ref, Temporin1Ec FLPVIAGLLSKLF 2647 (XXA, frog) AP00869 Ref, Temporin 1JaILPLVGNLLNDLL 2648 (XXA, Temporin- 1Ja, frog) AP00873 Ref, Temporin 1PraILPILGNLLNGLL 2649 (XXA, frog) AP00874 Ref, Temporin 1VE FLPLVGKILSGLI2650 (XXA, frog) AP00875 Ref, Temporin 1Va FLSSIGKILGNLL 2651 (XXA,frog) AP00876 Ref, Temporin 1Vb FLSIIAKVLGSLF 2652 (XXA, frog) AP00877Ref, Brevinin-1Ja FLGSLIGAAIPAIKQLLGLKK 2653 (frog) AP00878 Ref,Brevinin- FLPILASLAAKFGPKLFCLVTKKC 2654 1BYa (frog) AP00884 Ref,Ixosin-B (tick) QLKVDLWGTRSGIQPEQHSSGKSD 2655 VRRWRSRY AP00885 Ref,Brevinin- FLPILASLAAKLGPKLFCLVTKKC 2656 1BYb (frog) AP00886 Ref,Brevinin- FLPILASLAATLGPKLLCLITKKC 2657 1BYc (frog) AP00887 Ref,Brevinin- GILSTFKGLAKGVAKDLAGNLLDK 2658 2BYa (frog) FKCKITGC AP00888Ref, Brevinin- GIMDSVKGLAKNLAGKLLDSLKC 2659 2BYb (frog) KITGC AP00891Ref, Pilosulin 3 IIGLVSKGTCVLVKTVCKKVLKQG 2660 (Myr b III)(ants) AP00892Ref, Pilosulin 4 PDITKLNIKKLTKATCKVISKGASM 2661 (Myr b IV)(ants)CKVLFDKKKQE AP00893 Ref, Pilosulin 5 DVKGMKKAIKGILDCVIEKGYDKL 2662 (Myrb III)(ants) AAKLKKVIQQLWE AP00894 Ref, Ocellatin 4GLLDFVTGVGKDIFAQLIKQI 2663 (XXA, frog) AP00895 Ref, OH-CATHKRFKKFFKKLKNSVKKRAKKFFK 2664 (snake cathelicidin, KPRVIGVSIPF reptilecathelicidin, or elapid cathelicidins) AP00896 Ref, BF-CATHKRFKKFFKKLKKSVKKRAKKFFK 2665 (snake cathelicidin) KPRVIGVSIPF AP00897Ref, NA-CATH KRFKKFFKKLKNSVKKRAKKFFK 2666 (snake cathelicidin)KPKVIGVTFPF AP00898 Ref, Temporin-1Sa FLSGIVGMLGKLF 2667 (XXA, frog)AP00899 Ref, Temporin-1Sb FLPIVTNLLSGLL 2668 (XXA, frog) AP00900 Ref,Temporin-1Sc FLSHIAGFLSNLF 2669 (XXA, frog) AP00913 Ref, Ib-AMP1EWGRRCCGWGPGRRYCVRWC 2670 (IbAMP1, plant defensin) AP00914 Ref, Ib-AMP2QYGRRCCNWGPGRRYCKRWC 2671 (IBAMP2, plant defensin) AP00915 Ref, Ee-CBPQQCGRQAGNRRCANNLCCSQYGY 2672 (EeCBP, plant CGRTNEYCCTSQGCQSQCRRCGdefensin, hevein- type, E. europaeus chitin-binding protein) AP00916Ref, Pa-AMP1 AGCIKNGGRCNASAGPPYCCSSYC 2673 (PaAMP1, plant FQIAGQSYGVCKNRdefensin, C6 type) AP00917 Ref, Pa-AMP2 ACIKNGGRCVASGGPPYCCSNYCL 2674(PaAMP2, plant QIAGQSYGVCKKH defensin, C6 type) AP00924 Ref,Ornithodoros GYGCPFNQYQCHSHCRGIRGYKG 2675 defensin B (softGYCTGRFKQTCKCY ticks) AP00925 Ref, Ornithodoros GYGCPFNQYQCHSHCSGIRGYKGG2676 defensin C (soft YCKGLFKQTCNCY ticks) AP00926 Ref, OrnithodorosGFGCPFNQYECHAHCSGVPGYKG 2677 defensin D (soft GYCKGLFKQTCNCY ticks)AP00927 Ref, IYFIADKMGIQLAPAWYQDIVNWV 2678 ButyrivibriocinSAGGTLTTGFAIIVGVTVPAWIAEA AR10 (XXC, class AAAFGIASA IV bacteriocin,gram-positive bacteria) AP00929 Ref, AS-48 ASLQFLPIAHMAKEFGIPAAVAGT 2679(enterocin 4, XXC, VINVVEAGGWVTTIVSILTAVGSG class IV bacteriocinGLSLLAAAGRESIKAYLKKEIKKK or class IId GKRAVIAW bacteriocin, Gram-positive bacteria) AP00930 Ref, Reutericin 6 IYWIADQFGIHLATGTARKLLDAM2680 (XXC, XXD1, ASGASLGTAFAAILGVTLPAWALA class IV AAGALGATAAbacteriocin, Gram- positive bacteria) AP00931 Ref, UberolysinLAGYTGIASGTAKKVVDAIDKGAA 2681 (XXC, class IV AFVIISIISTVISAGALGAVSASADFIbacteriocin, Gram- ILTVKNYISRNLKAQAVIW positive bacteria) AP00932 Ref,Acidocin B IYWIADQFGIHLATGTARKLLDAV 2682 (XXC, class IVASGASLGTAFAAILGVTLPAWALA bacteriocin, Gram- AAGALGATAA positivebacteria) AP00980 Ref, Phormia ATCDLLSGTGINHSACAAHCLLRG 2683 defensin B(insect NRGGYCNRKGVCVCRN defensin B) AP00990 Ref, Pth-St1 (plantRNCESLSHRFKGPCTRDSN 2684 defensin) AP00991 Ref, Snakin-1GSNFCDSKCKLRCSKAGLADRCLK 2685 (StSN1, plant YCGICCEECKCVPSGTYGNKHECPdefensin) CYRDKKNSKGKSKCP AP00992 Ref, Snakin-2 YSYKKIDCGGACAARCRLSSRPRL2686 (StSN2, plant CNRACGTCCARCNCVPPGTSGNTE defensin) TCPCYASLTTHGNKRKCPAP00993 Ref, So-D2 (S. oleracea GIFSSRKCKTPSKTFKGICTRDSNC 2687 defensinDTSCRYEGYPAGDCKGIRRRCMCS D2, plant defensin) KPC AP00994 Ref, So-D6 (S.oleracea GIFSNMYARTPAGYFRGP 2688 defensin D6, plant defensin) AP00997Ref, Nisin Q ITSISLCTPGCKTGVLMGCNLKTAT 2689 (lantibiotic, CNCSVHVSKbacteriocins, bacteria) AP01008 Ref, TachystatinYSRCQLQGFNCVVRSYGLPTIPCC 2690 A1 (BBS, RGLTCRSYFPGSTYGRCQRF horseshoecrabs) AP01009 Ref, Tachystatin C DYDWSLRGPPKCATYGQKCRTWS 2691 (BBS,horseshoe PRNCCWNLRCKAFRCRPR crabs) AP01012 Ref, Latarcin 3aSWKSMAKKLKEYMEKLKQRA 2692 (Ltc3a, XXA, BBM, spider) AP01013 Ref,Latarcin 3b SWASMAKKLKEYMEKLKQRA 2693 (Ltc3b, XXA, BBM, spider) AP01014Ref, Latarcin 4a GLKDKFKSMGEKLKQYIQTWKAKF 2694 (Ltc4a, XXA, BBM, spider)AP01015 Ref, Latarcin 4b SLKDKVKSMGEKLKQYIQTWKAKF 2695 (Ltc4b, XXA, BBM,spider) AP01016 Ref, Latarcin 5 GFFGKMKEYFKKFGASFKRRFANL 2696 (Ltc5,XXA, BBM, KKRL spider) AP01018 Ref, Latarcin 6a QAFQTFKPDWNKIRYDAMKMQTS2697 (Ltc6a, BBM, LGQMKKRFNL spider) AP01019 Ref, Latarcin 7GETFDKLKEKLKTFYQKLVEKAED 2698 (Ltc7, BBM, LKGDLKAKLS spider) AP01049Ref, Kalata B2 VCGETCFGGTCNTPGCSCTWPICT 2699 (plant cyclotides, RDGLPXXC) AP01141 Ref, Cryptdin-6 LRDLVCYCRARGCKGRERMNGTC 2700 (Crp6, animalRKGHLLYMLCCR defensin, alpha, mouse) AP01142 Ref, Rabbit kidneyKPYCSCKWRCGIGEEEKGICHKFPI 2701 defensin RK-2 VTYVCCRRP (animal defensin,alpha-defensin) AP01146 Ref, Gallinacin 6 DTLACRQSHGSCSFVACRAPSVDI 2702(Gal6, Gal-6, avian GTCRGGKLKCCKWAPSS beta defensin, bird) AP01147 Ref,Gallinacin 8 DTVACRIQGNFCRAGACPPTFTISG 2703 (Gal8, Gal-8, avianQCHGGLLNCCAKIPAQ beta defensin, bird) AP01148 Ref, Gallinacin 3IATQCRIRGGFCRVGSCRFPHIAIGK 2704 (Gal3, Gal-3, avian CATFISCCGRAY betadefensin, bird) AP01152 Ref, Lactococcin Q SIWGDIGQGVGKAAYWVGKAMG 2705(class IIb NMSDVNQASRINRKKKH bacteriocin, bacteria, chain a. For chainb, see Info) AP01155 Ref, Enterocin ESVFSKIGNAVGPAAYWILKGLGN 2706 1071(Ent1071A, MSDVNQADRINRKKH class IIb bacteriocin, bacteria; chain B isEnterocin 1071B or Ent1071B, see info) AP01156 Ref, Plantaricin SNKLAYNMGHYAGKATIFGLAAW 2707 (chain a, class IIb ALLA bacteriocin,bacteria) AP01159 Ref, Hinnavin II KWKIFKKIEHMGQNIRDGLIKAGP 2708 (HinII, XXA, AVQVVGQAATIYK insect) AP01160 Ref, NK-2KILRGLCKKIMRSFLRRISWDILTG 2709 (synthetic, XXA) KK AP01167 Ref,Plantaricin LTTKLWSSWGYYLGKKARWNLK 2710 NC8 (PLNC8, HPYVQF chain a,class IIb bacteriocin, bacteria. For chain b, see Info) AP01168 Ref,Carnocyclin A LVAYGIAQGTAEKVVSLINAGLTV 2711 (a circularGSIISILGGVTVGLSGVFTAVKAAI bacteriocin, XXC, AKQGIKKAIQL bacteria)AP01169 Ref, Lactacin F NRWGDTVLSAASGAGTGIKACKSF 2712 (LafX, class IIbGPWGMAICGVGGAAIGGYFGYTHN bacteriocin, bacteria. For LafA, see Info)AP01170 Ref, Brochocin C YSSKDCLKDIGKGIGAGTVAGAAG 2713 (BrcC, chainBrcA, GGLAAGLGAIPGAFVGAHFGVIGG class IIb SAACIGGLLGN bacteriocin,bacteria. For BrcB, see Info) AP01171 Ref, ThermophilinYSGKDCLKDMGGYALAGAGSGAL 2714 13 (chain a ThmA, WGAPAGGVGALPGAFVGAHVGAI2-chain class IIb AGGFACMGGMIGNKFN bacteriocin, bacteria. For chain BThmB, see Info) AP01172 Ref, ABP-118 KRGPNCVGNFLGGLFAGAAAGVP 2715 (chaina: LGPAGIVGGANLGMVGGALTCL Abp118alpha, class IIb bacteriocin, bacteria.For chain b: Abp118beta, see Info) AP01173 Ref, Salivaricin PKRGPNCVGNFLGGLFAGAAAGVP 2716 (chain a: Sln1; LGPAGIVGGANLGMVGGALTCLclass IIb bacteriocin, bacteria. For chain b: Sln2, see Info) AP01174Ref, Mutacin IV KVSGGEAVAAIGICATASAAIGGL 2717 (chain a: NlmA,AGATLVTPYCVGTWGLIRSH class IIb bacteriocin, bacteria. For chain b: NLmB,see Info) AP01175 Ref, Lactocin 705 GMSGYIQGIPDFLKGYLHGISAAN 2718 (chaina: KHKKGRLGY Lac705alpha; class IIb bacteriocin, bacteria. For chain b:Lac705beta, see Info) AP01176 Ref, Cytolysin TTPACFTIGLGVGALFSAKFC 2719(CylLS, bacteria; Chain B: CylLL) AP01177 Ref, Plantaricin EFFNRGGYNFGKSVRHVVDAIGSVA 2720 (chain a. PlnE, GILKSIR class IIbbacteriocin, bacteria. Chain b: PlnF) AP01178 Ref, Plantaricin JKGAWKNFWSSLRKGFYDGEAGRAI 2721 (chain a: PlnJ; class RR IIb bacteriocin,bacteria. Chain b: PlnK) AP01179 Ref, Enterocin SE-NGVYCNKQKCWVDWSRARSEIID 2722 K4 (class IIa RGVKAYVNGFTKVLGGIGGRbacteriocin, bacteria) AP01180 Ref, Acidocin NPKVAHCASQIGRSTAWGAVSGA2723 J1132 (class IIb bacteriocin, bacteria) AP01181 Ref, CurvaticinAYPGNGVHCGKYSCTVDKQTAIG 2724 L442 (class IIa NIGNNAA bacteriocin,bacteria) AP01182 Ref, Bacteriocin 32 FTPSVSFSQNGGVVEAAAQRGYIY 2725 (Bac32, class IIa KKYPKGAKVPNKVKMLVNIRGKQ bacteriocin,TMRTCYLMSWTASSRTAKYYYYI bacteria) AP01183 Ref, Bacteriocin 43ATYYGNGLYCNKEKCWVDWNQA 2726 (Bac 43, KGEIGKIIVNGWVNHGPWAPRR bacteriocin,bacteria) AP01184 Ref, Bacteriocin T8 ATYYGNGLYCNKEKCWVDWNQA 2727 (BacT8, class IIa KGEIGKIIVNGWVNHGPWAPRR bacteriocin, bacteria) AP01185 Ref,Enterocin B ENDHRMPNNLNRPNNLSKGGAKC 2728 (EntB, bacteriocin,GAAIAGGLFGIPKGPLAWAAGLAN bacteria) VYSKCN AP01186 Ref, Acidocin AKTYYGTNGVHCTKKSLWGKVRLK 2729 (bacteriocin, NVIPGTLCRKQSLPIKQDLKILLGWbacteria) ATGAFGKTFH AP01187 Ref, Enterocin Q MNFLKNGIAKWMTGAELQAYKK2730 (EntQ, class IIc KYGCLPWEKISC bacteriocin, leaderless, i.e. nosignal peptide, bacteria) AP01188 Ref, EnterocinMLAKIKAMIKKFPNPYTLAAKLTT 2731 EJ97 (EntEJ97, YEINWYKQQYGRYPWERPVA classIIc bacteriocin, leaderless, i.e. no signal peptide, bacteria) AP01189Ref, Enterocin RJ- APAGLVAKFGRPIVKKYYKQIMQF 2732 11 (EntRJ-11, classIGEGSAINKIIPWIARMWRT IIc bacteriocin, leaderless, i.e. no signalsequence, bacteria) AP01190 Ref, Enterocin L50 MGAIAKLVAKFGWPIVKKYYKQI2733 (old name: MQFIGEGWAINKIIEWIKKHI pediocin L50, EntL50A, a two-chain class IIc bacteriocin, leaderless, i.e. no signal peptide,bacteria. The sequence of EntL50B is provided in Info) AP01191 Ref, MR10MGAIAKLVAKFGWPIVKKYYKQI 2734 (MR10A, class IIc MQFIGEGWAINKIIDWIKKHIbacteriocin, leaderless, i.e. no signal peptide, bacteria. For thesequence of chain b, see Info) AP01192 Ref, Halocin S8SDCNINSNTAADVILCFNQVGSCA 2735 (HalS8, LCSPTLVGGPVP microhalocin,archaeocins, archeae) AP01193 Ref, Halocin C8 DIDITGCSACKYAAGQVCTIGCSA2736 (HalC8, AGGFICGLLGITIPVAGLSCLGFVEI microhalocins,VCTVADEYSGCGDAVAKEACNRA archaeocins, GLC archaea) AP01194 Ref, Lacticin3147 CSTNTFSLSDYWGNNGAWCTLTH 2737 (chain A1, a two- ECMAWCK chainlantibiotic, bacteriocin, bacteria. The sequence of chain A2 is given inInfo; XXD3) AP01195 Ref, Salivaricin A KRGSGWIATITDDCPNSVFVCC 2738(SalA, lantibiotic, bacteriocin, bacteria) AP01196 Ref, Microcin E492ATYYGNGLYCNKEKCWVDWNQA 2739 (MccE492, class KGEIGKIIVNGWVNHGPWAPRR IIbmicrocins, bacteriocin, bacteria; BBM; u- MccE492, siderophore peptide,BBI, XXG) AP01197 Ref, Hiracin JM79 ATYYGNGLYCNKEKCWVDWNQA 2740(HirJM79, a Sec- KGEIGKIIVNGWVNHGPWAPRR dependent class II bacteriocin,bacteria) AP01198 Ref, Thermophilin LSCDEGMLAVGGLGAVGGPWGA 2741 9(BlpDst, class IIb AVGVLVGAALYCF bacteriocin, bacteria. beta- chains:BlpUst, BlpEst, BapFst) AP01199 Ref, Penocin A KYYGNGVHCGKKTCYVDWGQAT2742 (PenA, class IIa ASIGKIIVNGWTQHGPWAHR bacteriocin, bacteria)AP01200 Ref, Salivaricin B GGGVIQTISHECRMNSWQFLFTCCS 2743 (SalB,lantibotic, bacteriocin, bacteria) AP01201 Ref, Lacticin 481KGGSGVIHTISHECNMNSWQFVFT 2744 (lantibiotic, class I CCS bacteriocin,bacteria) AP01202 Ref, Bacteriocin KGGSGVIHTISHEVIYNSWNFVFTC 2745 J46(BacJ46, CS bacteriocin, bacteria) AP01203 Ref, Nukacin AKKKSGVIPTVSHDCHMNSFQFVFT 2746 (NucA, Nukacin CCS ISK-1, NukISK-1,bacteriocin, bacteria) AP01204 Ref, StreptococcinGKNGVFKTISHECHLNTWAFLATC 2747 A-FF22 CS (LANTIBIOTIC, class Ibacteriocin, bacteria) AP01210 Ref, Jelleine-I PFKLSLHL 2748 (honeybees,insect, XXA) AP01211 Ref, Jelleine-II TPFKLSLHL 2749 (honeybees, insect,XXA) AP01212 Ref, Jelleine-III EPFKLSLHL 2750 (honeybees, insect, XXA)AP01213 Ref, EFRGSIVIQGTKEGKSRPSLDIDYK 2751 HymenoptaecinQRVYDKNGMTGDAYGGLNIRPGQ (honeybees, insect PSRQHAGFEFGKEYKNGFIKGQSEdefensin, XXcooh) VQRGPGGRLSPYFGINGGFRF AP01216 Ref, Ascaphin-1GFRDVLKGAAKAFVKTVAGHIAN 2752 (frog, XXA) AP01218 Ref, Ascaphin-3GFRDVLKGAAKAFVKTVAGHIANI 2753 (frog) AP01220 Ref, Ascaphin-5GIKDWIKGAAKKLIKTVASNIANQ 2754 (frog) AP01222 Ref, Ascaphin-7GFKDWIKGAAKKLIKTVASSIANQ 2755 (frog) AP01223 Ref, Ascaphin-8GFKDLLKGAAKALVKTVLF 2756 (frog, XXA) AP01226 Ref, Microcin C7 MRTGNAD2757 (MccC7, microcin C51, MccC51, class I microcins, bacteriocins,bacteria. Others: MccA; XXamp; BBPe) AP01227 Ref, Microcin B17VGIGGGGGGGGGGSCGGQGGGCG 2758 (MccB17, class I GCSNGCSGGNGGSGGSGSHImicrocins, bacteriocins, Gram- negative bacteria; BBPe) AP01228 Ref,Microcin V ASGRDIAMAIGTLSGQFVAGGIGA 2759 (MccV, (old name)AAGGVAGGAIYDYASTHKPNPAM Colicin V, ColV; SPSGLGGTIKQKPEGIPSEAWNYAA classII microcins, GRLCNWSPNNLSDVCL bacteriocins, Gram- negative bacteria)AP01229 Ref, Microcin L GDVNWVDVGKTVATNGAGVIGG 2760 (MccL, class IIaAFGAGLCGPVCAGAFAVGSSAAV microcins, AALYDAAGNSNSAKQKPEGLPPEAbacteriocins, Gram- WNYAEGRMCNWSPNNLSDVCL negative bacteria) AP01230Ref, Microcin M DGNDGQAELIAIGSLAGTFISPGFG 2761 (MccM, class IIbSIAGAYIGDKVHSWATTATVSPSM microcins, SPSGIGLSSQFGSGRGTSSASSSAGSbacteriocins, Gram- GS negative bacteria) AP01231 Ref, Microcin H47GGAPATSANAAGAAAIVGALAGIP 2762 (MccH47, class IIbGGPLGVVVGAVSAGLTTGIGSTVG microcins, SGSASSSAGGGS bacteriocins, Gram-negative bacteria) AP01232 Ref, Microcin I47 MNLNGLPASTNVIDLRGKDMGTYI2763 (MccI47, class IIb DANGACWAPDTPSIIMYPGGSGPS microcins,YSMSSSTSSANSGS bacteriocins, Gram- negative bacteria) Aibellin *Ac U A UA U A Q U F U G U U P V U U E E 2764 [NHC(CH2Ph)HCH2NHCH2CH2]OHAlamethicin_F-30 * Ac U P U A U A Q U V U G L U P V U U E Q F 2765 OHAlamethicin_F-50 * Ac U P U A U A Q U V U G L U P V U U Q Q F 2766 OHAlamethicin_II * Ac U P U A U U Q U V U G L U P V U U E Q F 2767 OHAmpullosporin * Ac W A U U L U Q U U U Q L U Q L OH 2768Ampullosporin_B * Ac W A U U L U Q A U U Q L U Q L OH 2769Ampullosporin_C * Ac W A U U L U Q U A U Q L U Q L OH 2770Ampullosporin_D * Ac W A U U L U Q U U A Q L U Q L OH 2771Ampullosporin_E1 * Ac W A U U L U Q A U U Q L A Q L OH 2772Ampullosporin_E2 * Ac W A U U L U Q U A A Q L U Q L OH 2773Ampullosporin_E3 * Ac W A U U L U Q U U A Q L A Q L OH 2774Ampullosporin_E4 * Ac W A U U L U Q A A U Q L U Q L OH 2775Antiamoebin_I * Ac F U U U J G L U U O Q J O U P F OH 2776Antiamoebin_II * Ac F U U U J G L U U O Q J P U P F OH 2777Antiamoebin_III * Ac F U U U U G L U U O Q J O U P F OH 2778Antiamoebin_IV * Ac F U U U J G L U U O Q J O U P F OH 2779Antiamoebin_V * Ac F U U U J A L U U O Q J O U P F OH 2780Antiamoebin_VI * Ac F U U U U G L U U O Q U O U P F OH 2781Antiamoebin_VII * Ac F A U J U G L U U O Q J O U P F OH 2782Antiamoebin_VIII * Ac F U U U J G L U U O Q U O U P F OH 2783Antiamoebin_IX * Ac F U A U J G L U U O Q J O U P F OH 2784Antiamoebin_X * Ac F U U U J G L J U O Q U O U P F OH 2785Antiamoebin_XI * Ac F U U U U A L U U O Q J O U P F OH 2786Antiamoebin_XII * Ac F U U U U G L A U O Q J O U P F OH 2787Antiamoebin_XIII * Ac V U U U U G L U U O Q J O U P F OH 2788Antiamoebin_XIV * Ac V U U U V G L U U O Q J O U P F OH 2789Antiamoebin_XV * Ac L U U U U G L U U O Q J O U P F OH 2790Antiamoebin_XVI * Ac L U U U J G L U U O Q J O U P F OH 2791Atroviridin_A * Ac U P U A U A Q U V U G L U P V U U Q Q F 2792 OHAtroviridin_B * Ac U P U A U A Q U V U G L U P V U J Q Q F 2793 OHAtroviridin_C * Ac U P U A U U Q U V U G L U P V U J Q Q F 2794 OHBergofungin_A * Ac V U U U V G L U U O Q J O U F OH 2795 Bergofungin_B *Ac V U U U V G L V U O Q U O U F OH 2796 Bergofungin_C * Ac V U U U V GL U U O Q U O U F OH 2797 Bergofungin_D * Ac V U U V G L U U O Q U O U FOH 2798 Boletusin * Ac F U A U J L Q G U U A A U P U U U Q W 2799 OHCephaibol_A * Ac F U U U U G L J U O Q J O U P F OH 2800 Cephaibol_A2 *Ac F U U U U A L J U O Q J O U P F OH 2801 Cephaibol_B * Ac F U U U J GL J U O Q J O U P F OH 2802 Cephaibol_C * Ac F U U U U G L J U O Q U O UP F OH 2803 Cephaibol_D * Ac F U U U U G L U U O Q U O U P F OH 2804Cephaibol_E * Ac F U U U U G L U U O Q J O U P F OH 2805 Cephaibol_P *Ac F J Q U I T U L U O Q U O U P F S OH 2806 Cephaibol_Q * Ac F J Q U IT U L U P Q U O U P F S OH 2807 Cervinin_1 * Ac L U P U L U P A U P V LOH 2808 Cervinin_2 * Ac L U P U L U P A U P V L OCOCH3 2809Chrysospermin_A * Ac F U S U U L Q G U U A A U P U U U Q W 2810 OHChrysospermin_B * Ac F U S U U L Q G U U A A U P J U U Q W 2811 OHChrysospermin_C * Ac F U S U J L Q G U U A A U P U U U Q W 2812 OHChrysospermin_D * Ac F U S U J L Q G U U A A U P J U U Q W 2813 OHClonostachin * Ac U O L J O L J O U J U O J I 2814O[CH(CH(OH)CH2OH)CH(OH)CH(OH)CH2]OH Emerimicin_II_A * Ac W I Q U I T U LU O Q U O U P F OH 2815 Emerimicin_II_B * Ac W I Q J I T U L U O Q U O UP F OH 2816 Emerimicin_III * Ac F U U U V G L U U O Q J O U F OH 2817Emerimicin_IV * Ac F U U U V G L U U O Q J O A F OH 2818Harzianin_HB_I * Ac U N L I U P J L U P L OH 2819 Harzianin_HC_I * Ac UN L U P S V U P U L U P L OH 2820 Harzianin_HC_III * Ac U N L U P S V UP J L U P L OH 2821 Harzianin_HC_IX * Ac U N L U P A I U P J L U P L OH2822 Harzianin_HC_VI * Ac U N L U P A V U P U L U P L OH 2823Harzianin_HC_VIII * Ac U N L U P A V U P J L U P L OH 2824Harzianin_HC_VIII * Ac U N L U P A V U P J L U P L OH 2825Harzianin_HC_X * Ac U Q L U P A V U P J L U P L OH 2826Harzianin_HC_XI * Ac U N L U P S I U P U L U P L OH 2827Harzianin_HC_XII * Ac U N L U P S I U P J L U P L OH 2828Harzianin_HC_XIII * Ac U Q L U P S I U P J L U P L OH 2829Harzianin_HC_XIV * Ac U N L U P A I U P U L U P L OH 2830Harzianin_HC_XV * Ac U Q L U P A I U P J L U P L OH 2831Harzianin_HK_VI * Ac U N I I U P L L U P L OH 2832 Harzianin_PCU4 * Ac UN L U P S I U P U L U P V OH 2833 Helioferin_A * Fa P ZZ A U I I U U AAE2834 Helioferin_B * Fa P ZZ A U I I U U AMAE 2835 Heptaibin * Ac F U U UV G L U U O Q U O U F OH 2836 Hypelcin_A * Ac U P U A U U Q L U G U U UP V U U Q Q L 2837 OH Hypelcin_A_I * Ac U P U A U U Q U L U G U U P V UU Q Q L 2838 OH Hypelcin_A_II * Ac U P U A U A Q U L U G U U P V U U Q QL 2839 OH Hypelcin_A_III * Ac U P U A U U Q U L U G U U P V U U Q Q 2840[C7H16NO] Hypelcin_A_IV * Ac U P U A U U Q U I U G U U P V U U Q Q L2841 OH Hypelcin_A-III * Ac U P U A U U Q U L U G U U P V U J Q Q L 2842OH Hypelcin_A-IX * Ac U P U A U U Q U I U G U U P V U J Q Q L 2843 OHHypelcin_A-V * Ac U P U A U U Q U L U G U U P V U U Q Q I 2844 OHHypelcin_A-VI * Ac U P U A U A Q U L U G U U P V U U Q Q I 2845 OHHypelcin_A-VII * Ac U P U A U A Q U L U G U U P V U J Q Q L 2846 OHHypelcin_A-VIII * Ac U P U A U A Q U I U G U U P V U U Q Q L 2847 OHHypelcin_B_I * Ac U P U A U U Q U L U G U U P V U U E Q L 2848 OHHypelcin_B_II * Ac U P U A U A Q U L U G U U P V U U E Q L 2849 OHHypelcin_B_III * Ac U P U A U U Q U L U G U U P V U J E Q L 2850 OHHypelcin_B_IV * Ac U P U A U U Q U I U G U U P V U U E Q L 2851 OHHypelcin_B_V * Ac U P U A U U Q U L U G U U P V U U E Q I 2852 OHHypomurocin_A_I * Ac U Q V V U P L L U P L OH 2853 Hypomurocin_A_II * AcJ Q V V U P L L U P L OH 2854 Hypomurocin_A_III * Ac U Q V L U P L I U PL OH 2855 Hypomurocin_A_IV * Ac U Q I V U P L L U P L OH 2856Hypomurocin_A_V * Ac U Q I I U P L L U P L OH 2857 Hypomurocin_A_Va * AcU Q I L U P L I U P L OH 2858 Hypomurocin_B_I * Ac U S A L U Q U V U G UU P L U U Q V OH 2859 Hypomurocin_B_II * Ac U S A L U Q U V U G U U P LU U Q L OH 2860 Hypomurocin_B_IIIa * Ac U A A L U Q U V U G U U P L U UQ V OH 2861 Hypomurocin_B_IIIb * Ac U S A L U Q J V U G U U P L U U Q VOH 2862 Hypomurocin_B_IV * Ac U S A L U Q U V U G J U P L U U Q V OH2863 Hypomurocin_B_V * Ac U S A L U Q U V U G J U P L U U Q L OH 2864Leul_Zervamicin * Ac L I Q J I T U L U O Q U O U P F OH 2865Longibrachin_A_I * Ac U A U A U A Q U V U G L U P V U U Q Q F 2866 OHLongibrachin_A_II * Ac U A U A U A Q U V U G L U P V U J Q Q F 2867 OHLongibrachin_A_III * Ac U A U A U U Q U V U G L U P V U U Q Q F 2868 OHLongibrachin_A_IV * Ac U A U A U U Q U V U G L U P V U J Q Q F 2869 OHLongibrachin_B_II * Ac U A U A U A Q U V U G L U P V U U E Q F 2870 OHLongibrachin_B_III * Ac U A U A U A Q U V U G L U P V U J E Q F 2871 OHLP237_F5 * Oc U P Y U Q Q U Zor Q A L OH 2872 LP237_F7 * Ac U P F U Q QU U Q A L OH 2873 LP237_F8 * Oc U P F U Q Q U Zor Q A L OH 2874 NA_VII *Ac U A A U J Q U U U S L U OCH3 2875 Paracelsin_A * Ac U A U A U A Q U VU G U U P V U U Q Q 2876 F OH Paracelsin_B * Ac U A U A U A Q U L U G UU P V U U Q Q F 2877 OH Paracelsin_C * Ac U A U A U U Q U V U G U U P VU U Q Q 2878 F OH Paracelsin_D * Ac U A U A U U Q U L U G U U P V U U QQ F 2879 OH Paracelsin_E * Ac U A U A U A Q U L U G U A P V U U Q Q F2880 OH Peptaibolin * Ac L U L U F OH 2881 Peptaivirin_A * Ac F U A U JL Q G U U A A U P J U U Q W 2882 OH Peptaivirin_B * Ac F U S U J L Q G UU A A U P J U U Q F OH 2883 Polysporin_A * Ac U P U A U U Q U V U G V UP V U U Q Q F 2884 OH Polysporin_B * Ac U P U A U U Q U V U G L U P V UU Q Q F 2885 OH Polysporin_C * Ac U P U A U U Q U I U G L U P V U U Q QF 2886 OH Polysporin_D * Ac U P U A U U Q U I U G L U P V U V Q Q F 2887OH Pseudokinin_KLIII * Ac U N I I U P L L U P NH2 2888Pseudokinin_KLVI * Ac U N I I U P L V hydroxyketopiperazine 2889Samarosporin_I * Ac F U U U V G L U U O Q J O A F OH 2890Samarosporin_II * Ac F U U U V G L U U O Q J O U F OH 2891Saturnisporin_SA_I * Ac U A U A U A Q U L U G U U P V U U Q Q F 2892 OHSaturnisporin_SA_II * Ac U A U A U A Q U L U G U U P V U J Q Q F 2893 OHSaturnisporin_SA_III * Ac U A U A U U Q U L U G U U P V U U Q Q F 2894OH Saturnisporin_SA_IV * Ac U A U A U U Q U L U G U U P V U J Q Q F 2895OH Stilbellin_I * Ac F U U U V G L U U O Q J O A F OH 2896Stilbellin_II * Ac F U U U V G L U U O Q J O U F OH 2897Stilboflavin_A_1 * Ac U P U A U A Q U V U G U U P V U U E Q V 2898 OHStilboflavin_A_2 * Ac U P U A U A Q U L U G U U P V U U E Q V 2899 OHStilboflavin_A_3 * Ac U P U A U U Q U V U G U A P V U U E Q L 2900 OHStilboflavin_A_4 * Ac U P U A U A Q U L U G U U P V U U E Q L 2901 OHStilboflavin_A_5 * Ac U P U A U U Q U L U G U U P V U U E Q V 2902 OHStilboflavin_A_6 * Ac U P U A U A Q U L U G U U P V U U E Q J 2903 OHStilboflavin_A_7 * Ac U P U A U U Q U L U G U U P V U U E Q I 2904 OHStilboflavin_B_1 * Ac U P U A U A Q U V U G U U P V U U Q Q 2905 V OHStilboflavin_B_2 * Ac U P U A U A Q U L U G U U P V U U Q Q V 2906 OHStilboflavin_B_3 * Ac U P U A U A Q U V U G U U P V U U Q Q L 2907 OHStilboflavin_B_4 * Ac U P U A U A Q U L U G U U P V U U Q Q L 2908 OHStilboflavin_B_5 * Ac U P U A U U Q U L U G U U P V U U Q Q V 2909 OHStilboflavin_B_6 * Ac U P U A U U Q U V U G U U P V U U Q Q 2910 V OHStilboflavin_B_7 * Ac U P U A U U Q U L U G U U P V U U Q Q L 2911 OHStilboflavin_B_8 * Ac U P U A U U Q U V U G U U P V U U Q Q L 2912 OHStilboflavin_B_9 * Ac U P U A U U Q U L U G U U P V U U Q Q I 2913 OHStilboflavin_B_10 * Ac U P U A U U Q U V U G U U P V U U Q Q I 2914 OHSuzukacillin * Ac U A U A U A Q U U U G L U P V U U Q Q F 2915 OHTrichobrachin_A-I * Ac U N L L U P L U U P L OH 2916Trichobrachin_A-II * Ac U N L L U P V L U P V OH 2917Trichobrachin_A-III * Ac U N V L U P L L U P V OH 2918Trichobrachin_A-IV * Ac U N L V U P L L U P V OH 2919Trichobrachin_B-I * Ac U N L L U P V U V P L OH 2920Trichobrachin_B-II * Ac U N V L U P L U V P L OH 2921Trichobrachin_B-III * Ac U N L V U P L U V P L OH 2922Trichobrachin_B-IV * Ac U N L L U P L U V P V OH 2923Trichocellin_TC-A-I * Ac U A U A U A Q U L U G U U P V U U Q Q F 2924 OHTrichocellin_TC-A-II * Ac U A U A U A Q U L U G U U P V U J Q Q F 2925OH Trichocellin_TC-A-III * Ac U A U A U A Q U I U G U U P V U U Q Q F2926 OH Trichocellin_TC-A-IV * Ac U A U A U A Q U I U G U U P V U J Q QF 2927 OH Trichocellin_TC-A-V * Ac U A U A U A Q U L U G L U P V U U Q QF 2928 OH Trichocellin_TC-A-VI * Ac U A U A U A Q U L U G L U P V U J QQ F 2929 OH Trichocellin_TC-A- * Ac U A U A U A Q U I U G L U P V U U QQ F 2930 VII OH Trichocellin_TC-A- * Ac U A U A U A Q U I U G L U P V UJ Q Q F 2931 VIII OH Trichocellin_TC-B-I * Ac U A U A U A Q U L U G U UP V U U E Q F 2932 OH Trichocellin_TC-B-II * Ac U A U A U A Q U L U G UU P V U J E Q F 2933 OH Trichodecenin_TD_I * (Z)-4-decenoyl G G L U G IL OH 2934 Trichodecenin_TD_II * (Z)-4-decenoyl G G L U G L L OH 2935Trichogin_A_IV * Oc U G L U G G L U G I L OH 2936 Trichokindin_Ia * Ac US A U U Q J L U A U U P L U U Q I OH 2937 Trichokindin_Ib * Ac U S A U JQ U L U A U U P L U U Q I OH 2938 Trichokindin_IIa * Ac U S A U U Q U LU A J U P L U U Q I OH 2939 Trichokindin_IIb * Ac U S A U J Q J L U A UU P L U U Q L OH 2940 Trichokindin_IIIa * Ac U S A U U Q J L U A J U P LU U Q L OH 2941 Trichokindin_IIIb * Ac U S A U J Q U L U A J U P L U U QL OH 2942 Trichokindin_IV * Ac U S A U J Q J L U A U U P L U U Q I OH2943 Trichokindin_Va * Ac U S A U U Q J L U A J U P L U U Q I OH 2944Trichokindin_Vb * Ac U S A U J Q U L U A J U P L U U Q I OH 2945Trichokindin_VI * Ac U S A U J Q J L U A J U P L U U Q L OH 2946Trichokindin_VII * Ac U S A U J Q J L U A J U P L U U Q I OH 2947Trichokonin_Ia * Ac U A U A U A Q U V U G L A P V U U Q Q F 2948 OHTrichokonin_Ib * Ac U G U A U A Q U V U G L U P V U U Q Q F 2949 OHTrichokonin_IIa * Ac U A U A U A Q U V U G L U P A U U Q Q F 2950 OHTrichokonin_IIb * Ac A A U A U A Q U V U G L U P V U U Q Q F 2951 OHTrichokonin_IIc * Ac U A A A U A Q U V U G L U P V U U Q Q F 2952 OHTrichokonin_V * Ac U A U A U Q U V U G L U P V U U Q Q F 2953 OHTrichokonin_VII * Ac U A U A U A Q U V U G L U P V U J Q Q F 2954 OHTrichokonin_VIII * Ac U A U A U U Q U V U G L U P V U U Q Q F 2955 OHTrichokonin_IX * Ac U A U A U A Q U V U G L U P V U J Q Q F 2956 OHTricholongin_BI * Ac U G F U U Q U U U S L U P V U U Q Q L 2957 OHTricholongin_BII * Ac U G F U U Q U U U S L U P V U J Q Q L 2958 OHTrichopolyn_I * Fa P ZZ A U U I A U U AMAE 2959 Trichopolyn_II * Fa P ZZA U U V A U U AMAE 2960 Trichopolyn_III * Fa P ZZ A U U I A U A AMAE2961 Trichopolyn_IV * Fa P ZZ A U U V A U A AMAE 2962 Trichopolyn_V *Fa′ P ZZ A U U I A U U AMAE 2963 Trichorovin_TV_Ia * Ac U N V Lx U P LxLx U P V OH 2964 Trichorovin_TV_Ib * Ac U N V V U P Lx Lx U P Lx OH 2965Trichorovin_TV_IIa * Ac U N V V U P Lx Lx U P Lx OH 2966Trichorovin_TV_IIb * Ac U N Lx V U P Lx Lx U P V OH 2967Trichorovin_TV_IIIa * Ac U Q V V U P Lx Lx U P Lx OH 2968Trichorovin_TV_IIIb * Ac U Q V Lx U P Lx Lx U P V OH 2969Trichorovin_TV_IVa * Ac U Q V V U P Lx Lx U P Lx OH 2970Trichorovin_TV_IVb * Ac U Q Lx V U P Lx Lx U P V OH 2971Trichorovin_TV_IVc * Ac U N V Lx U P Lx Lx U P Lx OH 2972Trichorovin_TV_IXa * Ac U Q V Lx U P Lx Lx U P Lx OH 2973Trichorovin_TV_IXb * Ac U Q Lx Lx U P Lx Lx U P V OH 2974Trichorovin_TV_Va * Ac U N V Lx U P Lx Lx U P Lx OH 2975Trichorovin_TV_Vb * Ac U N Lx Lx U P Lx Lx U P V OH 2976Trichorovin_TV_VIa * Ac U N V Lx U P Lx Lx U P Lx OH 2977Trichorovin_TV_VIb * Ac U N Lx Lx U P Lx Lx U P V OH 2978Trichorovin_TV_VIIa * Ac U N Lx V U P Lx Lx U P Lx OH 2979Trichorovin_TV_VIIb * Ac U Q V Lx U P Lx Lx U P V OH 2980Trichorovin_TV_VIII * Ac U Q V Lx U P Lx Lx U P Lx OH 2981Trichorovin_TV_Xa * Ac U Q Lx V U P Lx Lx U P Lx OH 2982Trichorovin_TV_Xb * Ac U N Lx Lx U P Lx Lx U P Lx OH 2983Trichorovin_TV_XIIa * Ac U N I I U P L L U P I OH 2984Trichorovin_TV_XIIb * Ac U N Lx Lx U P Lx Lx U P L OH 2985Trichorovin_TV_XIII * Ac U Q Lx Lx U P Lx Lx U P Lx OH 2986Trichorovin_TV_XIV * Ac U Q Lx Lx U P Lx Lx U P Lx OH 2987Trichorozin_I * Ac U N I L U P I L U P V OH 2988 Trichorozin_II * Ac U QI L U P I L U P V OH 2989 Trichorozin_III * Ac U N I L U P I L U P L OH2990 Trichorozin_IV * Ac U Q I L U P I L U P L OH 2991Trichorzianine_TA_IIIc * Ac U A A U U Q U U U S L U P V U I Q Q W 2992OH Trichorzianine_TB_IIa * Ac U A A U U Q U U U S L U P L U I Q E W 2993OH Trichorzianine_TB_IIIc * Ac U A A U U Q U U U S L U P V U I Q E W2994 OH Trichorzianine_TB_IVb * Ac U A A U J Q U U U S L U P V U I Q E W2995 OH Trichorzianine_TB_Vb * Ac U A A U U Q U U U S L U P L U I Q E FOH 2996 Trichorzianine_TB_VIa * Ac U A A U J Q U U U S L U P L U I Q E FOH 2997 Trichorzianine_TB_VIb * Ac U A A U U Q U U U S L U P V U I Q E F2998 OH Trichorzianine_TB_VII * Ac U A A U J Q U U U S L U P V U I Q E FOH 2999 Trichorzin_HA_I * Ac U G A U U Q U V U G L U P L U U Q L OH 3000Trichorzin_HA_II * Ac U G A U U Q U V U G L U P L U J Q L OH 3001Trichorzin_HA_III * Ac U G A U J Q U V U G L U P L U U Q L OH 3002Trichorzin_HA_V * Ac U G A U J Q U V U G L U P L U J Q L OH 3003Trichorzin_HA_VI * Ac U G A U J Q J V U G L U P L U J Q L OH 3004Trichorzin_HA_VII * Ac U G A U J Q V V U G L U P L U J Q L OH 3005Trichorzin_MA_I * Ac U S A U U Q U L U G L U P L U U Q V OH 3006Trichorzin_MA_II * Ac U S A U J Q U L U G L U P L U U Q V OH 3007Trichorzin_MA_III * Ac U S A U J Q J L U G L U P L U U Q V OH 3008Trichorzin_PA_II * Ac U S A U J Q U V U G L U P L U U Q W OH 3009Trichorzin_PA_IV * Ac U S A U J Q J V U G L U P L U U Q W OH 3010Trichorzin_PA_V * Ac U S A J J Q U V U G L U P L U U Q W OH 3011Trichorzin_PA_VI * Ac U S A U J Q U V U G L U P L U U Q F OH 3012Trichorzin_PA_VII * Ac U S A J J Q U V U G L U P L U U Q W OH 3013Trichorzin_PA_VIII * Ac U S A U J Q J V U G L U P L U U Q F OH 3014Trichorzin_PA_IX * Ac U S A J J Q U V U G L U P L U U Q F OH 3015Trichorzin_PAU4 * Ac U S A U U Q U V U G L U P L U U Q W OH 3016Trichosporin_TS-B- * Ac U A G U A U Q U Lx A A Vx A P V U Vx Q 3017 1a-1Q F OH Trichosporin_TS-B- * Ac U A G A U U Q U Lx A A Vx A P V U Vx Q3018 1a-2 Q F OH Trichosporin_TS-B- * Ac U A G A U U Q U Lx U G Lx A P VU A Q 3019 1b Q F OH Trichosporin_TS-B- * Ac U A S A U U Q U Lx U G Lx AP V U U Q Q 3020 1d F OH Trichosporin_TS-B- * Ac U A G A U U Q U Lx U GLx U P V U U Q 3021 1e Q F OH Trichosporin_TS-B-1f * Ac U A S A U U Q ULx U G Lx U P V U U Q Q 3022 F OH Trichosporin_TS-B- * Ac U A G A U U QU Lx U G Lx A P V U U Q 3023 1g Q F OH Trichosporin_TS-B- * Ac U A G A UU Q U Lx U G Lx U P V U Vx Q 3024 1h Q F OH Trichosporin_TS-B-Ia * Ac UA S A U U Q U L U G L U P V U U Q Q F 3025 OH Trichosporin_TS-B- * Ac UA A A U U Q U L U G L U P V U U Q Q F 3026 IIIa OH Trichosporin_TS-B- *Ac U A A A U U Q U I U G L U P V U A Q Q F 3027 IIIb OHTrichosporin_TS-B- * Ac U A A A A U Q U I U G L U P V U U Q Q F 3028IIIc OH Trichosporin_TS-B- * Ac U A A A U U Q U V U G L U P V U U Q Q F3029 IIId OH Trichosporin_TS-B- * Ac U A A A U U Q U L U G L U P V U J QQ F 3030 IVb OH Trichosporin_TS-B- * Ac U A U A U U Q U V U G L U P V UU Q Q F 3031 IVc OH Trichosporin_TS-B- * Ac U A A A U U Q U V U G L U PV U J Q Q F 3032 IVd OH Trichosporin_TS-B-V * Ac U A A A U U Q U I U G LU P V U U Q Q F 3033 OH Trichosporin_TS-B- * Ac U A U A U U Q U I U G LU P V U U Q Q F 3034 VIa OH Trichosporin_TS-B- * Ac U A A A U U Q U I UG L U P V U J Q Q F 3035 VIb OH Trichotoxin_A-40 * Ac U G U L U E U U UA U U P L U J Q V OH 3036 Trichotoxin_A-40_I * Ac U G U L U Q U U A A UU P L U U E V OH 3037 Trichotoxin_A-40_II * Ac U G U L U Q U U U A A U PL U U E V OH 3038 Trichotoxin_A-40_III * Ac U G U L U Q U U A A U U P LU J E V OH 3039 Trichotoxin_A-40_IV * Ac U G U L U Q U U U A U U P L U UE V OH 3040 Trichotoxin_A-40_V * Ac U G U L U Q U U U A U U P L U J E VOH 3041 Trichotoxin_A-40_Va * Ac U A U L U Q U U U A U U P L U U E V OH3042 Trichotoxin_A-50_E * Ac U G U L U Q U U U A A U P L U U Q V OH 3043Trichotoxin_A-50_F * Ac U G U L U Q U U A A A U P L U J Q V OH 3044Trichotoxin_A-50_G * Ac U G U L U Q U U U A A U P L U J Q V OH 3045Trichotoxin_A-50_H * Ac U A U L U Q U U U A A U P L U J Q V OH 3046Trichotoxin_A-50_I * Ac U G U L U Q U U U A U U P L U J Q V OH 3047Trichotoxin_A-50_J * Ac U A U L U Q U U U A U U P L U J Q V OH 3048Trichovirin-Ia * Ac U G A L A Q Vx V U G U U P L U U Q L 3049 OHTrichovirin-Ib * Ac U G A L U Q A V U G J U P L U U Q L OH 3050Trichovirin-IIa * Ac U G A L A Q U V U G J U P L U U Q L OH 3051Trichovirin-IIb * Ac U G A L U Q U V U G U U P L U U Q L OH 3052Trichovirin-IIc * Ac U G A L U Q Vx V U G U U P L U U Q L 3053 OHTrichovirin-IIIa * Ac U G A L U Q J V U G U U P L U U Q L OH 3054Trichovirin-IIIb * Ac U G A L J Q J U U G U U P L U U Q L OH 3055Trichovirin-IVa * Ac U G A L J Q J V U G U U P L U U Q L OH 3056Trichovirin-IVb * Ac U G A L U Q U V U G J U P L U U Q L OH 3057Trichovirin-V * Ac U G A L U Q J V U G J U P L U U Q L OH 3058Trichovirin-VIa * Ac U G A L U Q J L U G J U P L U U Q L OH 3059Trichovirin-VIb * Ac U G A L J Q J V U G J U P L U U Q L OH 3060Trikoningin_KA_V * Ac U G A U I Q U U U S L U P V U I Q Q L OH 3061Trikoningin_KB_I * Oc U G V U G G V U G I L OH 3062 Trikoningin_KB_II *Oc J G V U G G V U G I L OH 3063 Tylopeptin_A * Ac W V U J A Q A U S U AL U Q L OH 3064 Tylopeptin_B * Ac W V U U A Q A U S U A L U Q L OH 3065XR586 * Ac W J Q U I T U L U P Q U O J P F G OH 3066 Zervamicin_A-1-16 *Boc W I A U I V U L U P A U P U P F OCH3 3067 Zervamicin_ZIA * Ac W I EJ V T U L U O Q U O U P F OH 3068 Zervamicin_ZIB * Ac W V E J I T U L UO Q U O U P F OH 3069 Zervamicin_ZIB′ * Ac W I E U I T U L U O Q U O U PF OH 3070 Zervamicin_ZIC * Ac W I E J I T U L U O Q U O U P F OH 3071Zervamicin_ZII-1 * Ac W I Q U V T U L U O Q U O U P F OH 3072Zervamicin_ZII-2 * Ac W I Q U I T U V U O Q U O U P F OH 3073Zervamicin_ZII-3 * Ac W V Q U I T U L U O Q U O U P F OH 3074Zervamicin_ZII-4 * Ac W I Q J V T U L U O Q U O U P F OH 3075Zervamicin_ZII-5 * Ac W I Q J I T U V U O Q U O U P F OH 3076Zervamicin_ZIIA * Ac W I Q U I T U L U O Q U O U P F OH 3077Zervamicin_ZIIB * Ac W I Q J I T U L U O Q U O U P F OH 3078 CAMEL135GWRLIKKILRVFKGL 3079 (CAM135) Novispirin G2 KNLRIIRKGIHIIKKY* 3080 B-33FKKFWKWFRRF 3081 B-34 LKRFLKWFKRF 3082 B-35 KLFKRWKHLFR 3083 B-36RLLKRFKHLFK 3084 B-37 FKTFLKWLHRF 3085 B-38 IKQLLHFFQRF 3086 B-39KLLQTFKQIFR 3087 B-40 RILKELKNLFK 3088 B-41 LKQFVHFIHRF 3089 B-42VKTLLHIFQRF 3090 B-43 KLVEQLKEIFR 3091 B-44 RVLQEIKQILK 3092 B-45VKNLAELVHRF 3093 B-46 ATHLLHALQRF 3094 B-47 KLAENVKEILR 3095 B-48RALHEAKEALK 3096 B-49 FHYFWHWFHRF 3097 B-50 LYHFLHWFQRF 3098 B-51YLFQTWQHLFR 3099 B-52 YLLTEFQHLFK 3100 B-53 FKTFLQWLHRF 3101 B-54IKTLLHFFQRF 3102 B-55 KLLQTFNQIFR 3103 B-56 TILQSLKNIFK 3104 B-57LKQFVKFIHRF 3105 B-58 VKQLLKIFNRF 3106 B-59 KLVQQLKNIFR 3107 B-60RVLNQVKQILK 3108 B-61 VKKLAKLVRRF 3109 B-62 AKRLLKVLKRF 3110 B-63KLAQKVKRVLR 3111 B-64 RALKRIKHVLK 3112 1C-1 RRRRWWW 3113 1C-2 RRWWRRW3114 1C-3 RRRWWWR 3115 1C-4 RWRWRWR 3116 2C-1 RRRFWWR 3117 2C-2 RRWWRRF*3118 2C-3 RRRWWWF* 3119 2C-4 RWRWRWF* 3120 3C-1 RRRRWWK 3121 3C-2RRWWRRK 3122 3C-3 RRRWWWK 3123 3C-4 RWRWRWK 3124 4C-1 RRRKWWK 3125 4C-2RRWKRRK 3126 4C-3 RRRKWWK 3127 4C-4 RWRKRWK 3128 a-3 LHLLHQLLHLLHQF*3129 a-4 AQAAHQAAHAAHQF* 3130 a-5 KLKKLLKKLKKLLK 3131 a-6LKLLKKLLKLLKKF* 3132 a-7 LQLLKQLLKLLKQF* 3133 a-8 AQAAKQAAKAAKQF* 3134a-9 RWRRWWRHFHHFFH* 3135 a-10 KLKKLLKRWRRWWR 3136 a-11 RWRRLLKKLHHLLH*3137 a-12 KLKKLLKHLHHLLH* 3138 BD-1 FVF RHK WVW KHR FLF 3139 BD-2 VFIHRH VWV HKH VLF 3140 BD-3 WR WR AR WR WR LR WR F 3141 BD-4 WR IH LR ARLH VK FR F 3142 BD-5 LR IH AR FK VH IR LK F 3143 BD-6 FH IK FR VH LK VRFH F 3144 BD-7 FH VK IH FR LH VK FH F 3145 BD-8 LH IH AH FH VH IH LH F3146 BD-9 FK IH FR LK VH IR FK F 3147 BD-10 FK AH IR FK LR VK FH F 3148BD-11 LK AK IK FK VK LK IK F 3149 BD-12 WIW KHK FL HRH FLF 3150 BD-13VFL HRH VI KHK LVF 3151 BD-14 FL HKH VL RHR IVF 3152 BD-15 VF KHK IV HRHILF 3153 BD-16 FLF KH LFL HR IFF 3154 BD-17 LF KH ILI HR VIF 3155 BD-18FL HKH LF KHK LF 3156 BD-19 VF RHR FI HRH VF 3157 BD-20 FI HK LV HKH VLF3158 BD-21 VL RH LF RHR IVF 3159 BD-22 LV HK LIL RH LLF 3160 BD-23 VF KRVLI HK LIF 3161 BD-24 IV RK FLF RHK VF 3162 BD-25 VL KH VIA HKR LF 3163BD-26 FI RK FLF KH LF 3164 BD-27 VI RH VWV RK LF 3165 BD-28 FLF RHR FRHR LVF 3166 BD-29 LFL HKH A KHK FLF 3167 BD-30 F KHK F KHK FIF 3168BD-31 L RHR L RHR LIF 3169 BD-32 LIL K FLF K FVF 3170 BD-33 VLI R ILV RVIF 3171 BD-34 F RHR F RHR F 3172 BD-35 L KHK L KHK F 3173 BD-36 F K FKHK LIF 3174 BD-37 L R L RHR VLF 3175 BD-38 F K FLF K FLF 3176 BD-39 L RLFL R WLF 3177 BD-40 F K FLF KHK F 3178 BD-41 L R LFL RHR F 3179 BD-42 FK FLF K F 3180 BD-43 L R LFL R F 3181 AA-1 HHFFHHFHHFFHHF* 3182 AA-2FHFFHHFFHFFHHF* 3183 AA-3 KLLK-GAT-FHFFHHFFHFFHHF 3184 AA-4KLLK-FHFFHHFFHFFHHF 3185 AA-5 FHFFHHFFHFFHHFKLLK 3186 RIP YSPWTNF* 3187Lariatin A c(Gly-Ser-Gln-Leu-Val-Tyr-Arg-Glu)-Trp-Val- 3188(anti-mycobacteria) Gly-His-Ser-Asn-Val-Ile-Lys-Pro Lariatin Bc(Gly-Ser-Gln-Leu-Val-Tyr-Arg-Glu)-Trp-Val- 3189 (anti-mycobacteria)Gly-His-Ser-Asn-Val-Ile-Lys-Gly-Pro-Pro Abreviations: U -Aminoisobutyric Acid (Aib); J - Isovaline (Iva); O - Hydroxyproline(Hyp); Z - Ethylnorvaline (EtNor); x or xx means L or I at thatposition; Ac - optionally acetylated N-term; OH, OCH3 - optional C-term;Alkane long chains are noted in brackets; *optionally amidatedC-terminus. Where protecting groups are shown, the gropus are optional.Conversely any of the peptides shown without protecting groups can,optionally bear one or more protecting groups. Where peptides are showncircularized, linear forms are also contemplated. Conversely, wherelinear peptides are shown circularlized versions are also contemplated.

In certain embodiments the antimicrobial peptide consists of orcomprises the amino acid sequence of LL-37 (LLGDFFRK SKEKIGKEFKRIVQRIKDFLRNL VPRTES, SEQ ID NO:3190) or a variant of LL-37. LL-37 is acathelicidin anti-microbial corresponding to amino acids 134-170 of thehuman cationic antimicrobial protein 18 (hCAP18). In certain embodimentsthe antimicrobial peptide consists of or comprises the amino acidsequence of an LL-37 variant as described in U.S. Patent Publication No:2009/0156499 A1). Illustrative variants comprise or consist of the aminoacid sequence having at least 90%, 95%, or 98% sequence identity withthe amino acid sequence FKRIVQRIKDFLRX₁ (SEQ ID NO:3191), where X₁ isselected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, and 8amino acids. In certain embodiments illustrative variants comprise orconsist of the amino acid sequence having at least 90%, 95%, or 98%sequence identity with the amino acid sequence X₁RLFDKIRQVIRKFX₂ (SEQ IDNO:3192) where X₁ is 0, 1, 2, 3, 4, 5, 6, 7, or 8 amino acids and X₂ is0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 amino acids.

In certain embodiments the antimicrobial peptide consists of orcomprises the amino acid sequence of an LL-37 variant shown in Table 15.

TABLE 15 LL-37 peptide and variants. SEQ ID Amino acid sequence ID NOLL-37 LLGDFFRKSKEKIGKEFKRIVQRIKDFLR 3193 NLVPRTES Cys-LL-37CLLGDFFRKSKEKIGKEFKRIVQRIKDF 3194 LRNLVPRTES LL-37(17-32)FKRIVQRIKDFLRNLV 3195 Cys-LL-37-Cys CLLGDFFRKSKEKIGKEFKRIVQRIKDFL 3196RNLVPRTESC LL-37FK-13 FKRIVQRIKDFLR 3197 LL-37FKR FKRIVQRIKDFLRNLVPRTES3198 LL-37GKE GKEFKRIVQRIKDFLRNLVPR 3199 LL-37KRI KRIVQRIKDFLRNLVPRTES3200 LL-37LLG LLGDFFRKSKEKIGKEFKRIV 3201 LL-37RKSRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES 3202 LL-37SKE SKEKIGKEFKRIVQRIKDFLR 3203LL-37-Cys LLGDFFRKSKEKIGKEFKRIVQRIKDFL 3204 RNLVPRTESC

A number of antimicrobial peptides are also disclosed in U.S. Pat. Nos.7,271,239, 7,223,840, 7,176,276, 6,809,181, 6,699,689, 6,420,116,6,358,921, 6,316,594, 6,235,973, 6,183,992, 6,143,498, 6,042,848,6,040,291, 5,936,063, 5,830,993, 5,428,016, 5,424,396, 5,032,574,4,623,733, which are incorporated herein by reference for the disclosureof particular antimicrobial peptides.

v. Ligands.

In certain embodiments the effector can comprise one or more ligands,epitope tags, and/or antibodies. In certain embodiments preferredligands and antibodies include those that bind to surface markers onimmune cells. Chimeric moieties utilizing such antibodies as effectormolecules act as bifunctional linkers establishing an associationbetween the immune cells bearing binding partner for the ligand orantibody and the target microorganism(s).

The terms “epitope tag” or “affinity tag” are used interchangeablyherein, and used refers to a molecule or domain of a molecule that isspecifically recognized by an antibody or other binding partner. Theterm also refers to the binding partner complex as well. Thus, forexample, biotin or a biotin/avidin complex are both regarded as anaffinity tag. In addition to epitopes recognized in epitope/antibodyinteractions, affinity tags also comprise “epitopes” recognized by otherbinding molecules (e.g. ligands bound by receptors), ligands bound byother ligands to form heterodimers or homodimers, His₆ bound by Ni-NTA,biotin bound by avidin, streptavidin, or anti-biotin antibodies, and thelike.

Epitope tags are well known to those of skill in the art. Moreover,antibodies specific to a wide variety of epitope tags are commerciallyavailable. These include but are not limited to antibodies against theDYKDDDDK (SEQ ID NO:3205) epitope, c-myc antibodies (available fromSigma, St. Louis), the HNK-1 carbohydrate epitope, the HA epitope, theHSV epitope, the His₄ (SEQ ID NO:3206), His_(s) (SEQ ID NO:3207), andHis₆ (SEQ ID NO:3208) epitopes that are recognized by the His epitopespecific antibodies (see, e.g., Qiagen), and the like. In addition,vectors for epitope tagging proteins are commercially available. Thus,for example, the pCMV-Tag1 vector is an epitope tagging vector designedfor gene expression in mammalian cells. A target gene inserted into thepCMV-Tag1 vector can be tagged with the FLAG® epitope (N-terminal,C-terminal or internal tagging), the c-myc epitope (C-terminal) or boththe FLAG (N-terminal) and c-myc (C-terminal) epitopes.

vi. Lipids and Liposomes.

In certain embodiments the effectors comprise one or more microparticlesor nanoparticles that can be loaded with an effector agent (e.g., apharmaceutical, a label, etc.). In certain embodiments themicroparticles or nanoparticles are lipidic particles. Lipidic particlesare microparticles or nanoparticles that include at least one lipidcomponent forming a condensed lipid phase. Typically, a lipidicnanoparticle has preponderance of lipids in its composition. Variouscondensed lipid phases include solid amorphous or true crystallinephases; isomorphic liquid phases (droplets); and various hydratedmesomorphic oriented lipid phases such as liquid crystalline andpseudocrystalline bilayer phases (L-alpha, L-beta, P-beta, Lc),interdigitated bilayer phases, and nonlamellar phases (see, e.g., TheStructure of Biological Membranes, ed. by P. Yeagle, CRC Press, BoraRaton, Fla., 1991). Lipidic microparticles include, but are not limitedto a liposome, a lipid-nucleic acid complex, a lipid-drug complex, alipid-label complex, a solid lipid particle, a microemulsion droplet,and the like. Methods of making and using these types of lipidicmicroparticles and nanoparticles, as well as attachment of affinitymoieties, e.g., antibodies, to them are known in the art (see, e.g.,U.S. Pat. Nos. 5,077,057; 5,100,591; 5,616,334; 6,406,713; 5,576,016;6,248,363; Bondi et al. (2003) Drug Delivery 10: 245-250; Pedersen etal., (2006) Eur. J. Pharm. Biopharm. 62: 155-162, 2006 (solid lipidparticles); U.S. Pat. Nos. 5,534,502; 6,720,001; Shiokawa et al. (2005)Clin. Cancer Res. 11: 2018-2025 (microemulsions); U.S. Pat. No.6,071,533 (lipid-nucleic acid complexes), and the like).

A liposome is generally defined as a particle comprising one or morelipid bilayers enclosing an interior, typically an aqueous interior.Thus, a liposome is often a vesicle formed by a bilayer lipid membrane.There are many methods for the preparation of liposomes. Some of themare used to prepare small vesicles (d<0.05 micrometer), some for largervesicles (d>0.05 micrometer). Some are used to prepare multilamellarvesicles, some for unilamellar ones. Methods for liposome preparationare exhaustively described in several review articles such as Szoka andPapahadjopoulos (1980) Ann. Rev. Biophys. Bioeng., 9: 467, Deamer andUster (1983) Pp. 27-51 In: Liposomes, ed. M. J. Ostro, Marcel Dekker,New York, and the like.

In various embodiments the liposomes include a surface coating of ahydrophilic polymer chain. “Surface-coating” refers to the coating ofany hydrophilic polymer on the surface of liposomes. The hydrophilicpolymer is included in the liposome by including in the liposomecomposition one or more vesicle-forming lipids derivatized with ahydrophilic polymer chain. In certain embodiments, vesicle-forminglipids with diacyl chains, such as phospholipids, are preferred. Oneillustrative phospholipid is phosphatidylethanolamine (PE), whichcontains a reactive amino group convenient for coupling to the activatedpolymers. One illustrative PE is distearoyl PE (DSPE). Another exampleis non-phospholipid double chain amphiphilic lipids, such as diacyl- ordialkylglycerols, derivatized with a hydrophilic polymer chain.

In certain embodiments a hydrophilic polymer for use in coupling to avesicle forming lipid is polyethyleneglycol (PEG), preferably as a PEGchain having a molecular weight between 1,000-10,000 Daltons, morepreferably between 1,000-5,000 Daltons, most preferably between2,000-5,000 Daltons. Methoxy or ethoxy-capped analogues of PEG are alsouseful hydrophilic polymers, commercially available in a variety ofpolymer sizes, e.g., 120-20,000 Daltons.

Other hydrophilic polymers that can be suitable include, but are notlimited to polylactic acid, polyglycolic acid, polyvinylpyrrolidone,polymethyloxazoline, polyethyloxazoline, polyhydroxypropylmethacrylamide, polymethacrylamide, polydimethylacrylamide, andderivatized celluloses, such as hydroxymethylcellulose orhydroxyethylcellulose.

Preparation of Lipid-Polymer Conjugates Containing these PolymersAttached to a suitable lipid, such as PE, have been described, forexample in U.S. Pat. No. 5,395,

The liposomes can, optionally be prepared for attachment to one or moretargeting moieties described herein. Here the lipid component includedin the liposomes would include either a lipid derivatized with thetargeting moiety, or a lipid having a polar-head chemical group, e.g.,on a linker, that can be derivatized with the targeting moiety inpreformed liposomes, according to known methods.

Methods of functionalizing lipids and liposomes with affinity moietiessuch as antibodies are well known to those of skill in the art (see,e.g., DE 3,218,121; Epstein et al. (1985) Proc. Natl. Acad. Sci., USA,82:3688 (1985); Hwang et al. (1980) Proc. Natl. Acad. Sci., USA, 77:4030; EP 52,322; EP 36,676; EP 88,046; EP 143,949; EP 142,641; Japanesepatent application 83-118008; U.S. Pat. Nos. 4,485,045 and 4,544,545;and EP 102,324, all of which are incorporated herein by reference).

vii. Agents that Physically Disrupt the Extracellular Matrix within aCommunity of Microorganisms

In certain embodiments, peptides can be coupled to agents thatphysically disrupt the extracellular matrix within a community ofmicroorganisms, for example a biofilm. In certain preferred embodiments,such an agent could be a bacterial cell-wall degrading enzyme, forexample SAL-2, or any species of glycosidase, alginase, peptidase,proteinase, lipase, or DNA or RNA degrading enzyme or compound, forexample rhRNase. Disruption of extracellular matrix of biofilms canresult in clearance and therapeutic benefit.

Peptides can also be attached to antimicrobial proteins, such as ProteinInhibitor C or Colicin, or fragments thereof, for example the IIa domainof Colicin, or the heparin-binding domain of Protein Inhibitor C.

viii. Polymeric Microparticles and/or Nanoparticles.

In certain embodiments the effector(s) comprise polymeric microparticlesand/or nanoparticles and/or micelles.

Microparticle and nanoparticle-based drug delivery systems haveconsiderable potential for treatment of various microorganisms.Technological advantages of polymeric microparticles or nanoparticlesused as drug carriers are high stability, high carrier capacity,feasibility of incorporation of both hydrophilic and hydrophobicsubstances, and feasibility of variable routes of administration,including oral application and inhalation. Polymeric nanoparticles canalso be designed to allow controlled (sustained) drug release from thematrix. These properties of nanoparticles enable improvement of drugbioavailability and reduction of the dosing frequency.

Polymeric nanoparticles are typically micron or submicron (<1 μm)colloidal particles. This definition includes monolithic nanoparticles(nanospheres) in which the drug is adsorbed, dissolved, or dispersedthroughout the matrix and nanocapsules in which the drug is confined toan aqueous or oily core surrounded by a shell-like wall. Alternatively,in certain embodiments, the drug can be covalently attached to thesurface or into the matrix.

Polymeric microparticles and nanoparticles are typically made frombiocompatible and biodegradable materials such as polymers, eithernatural (e.g., gelatin, albumin) or synthetic (e.g., polylactides,polyalkylcyanoacrylates), or solid lipids. In the body, the drug loadedin nanoparticles is usually released from the matrix by diffusion,swelling, erosion, or degradation. One commonly used material ispoly(lactide-co-glycolide) (PLG).

Methods of fabricating and loading polymeric nanoparticles ormicroparticles are well known to those of skill in the art. Thus, forexample, Matsumoto et al. (1999) Intl. J. Pharmaceutics, 185: 93-101teaches the fabrication of poly(L-lactide)-poly(ethyleneglycol)-poly(L-lactide) nanoparticles, Chawla et al. (2002) Intl. J.Pharmaceutics 249: 127-138, teaches the fabrication and use ofpoly(ε-caprolactone) nanoparticles delivery of tamifoxen, and Bodmeieret al. (1988) Intl. J. Pharmaceutics, 43: 179-186, teaches thepreparation of poly(D,L-lactide) microspheres using a solventevaporation method. “Intl. J. Pharmaceutics, 1988, 43, 179-186. Othernanoparticle formulations are described, for example, by Williams et al.(2003) J. Controlled Release, 91: 167-172; Leroux et al. (1996) J.Controlled Release, 39: 339-350; Soppimath et al. (2001) J. ControlledRelease, 70:1-20; Brannon-Peppas (1995) Intl. J. Pharmaceutics, 116:1-9; and the like.

C) Peptide Preparation.

The peptides described herein can be chemically synthesized usingstandard chemical peptide synthesis techniques or, particularly wherethe peptide does not comprise “D” amino acid residues, the peptide canbe recombinantly expressed. Where the “D” polypeptides are recombinantlyexpressed, a host organism (e.g. bacteria, plant, fungal cells, etc.)can be cultured in an environment where one or more of the amino acidsis provided to the organism exclusively in a D form. Recombinantlyexpressed peptides in such a system then incorporate those D aminoacids.

In certain embodiments, D amino acids can be incorporated inrecombinantly expressed peptides using modified amino acyl-tRNAsynthetases that recognize D-amino acids.

In certain embodiments the peptides are chemically synthesized by any ofa number of fluid or solid phase peptide synthesis techniques known tothose of skill in the art. Solid phase synthesis in which the C-terminalamino acid of the sequence is attached to an insoluble support followedby sequential addition of the remaining amino acids in the sequence is apreferred method for the chemical synthesis of the polypeptides of thisinvention. Techniques for solid phase synthesis are well known to thoseof skill in the art and are described, for example, by Barany andMerrifield (1963) Solid-Phase Peptide Synthesis; pp. 3-284 in ThePeptides: Analysis, Synthesis, Biology. Vol. 2: Special Methods inPeptide Synthesis, Part A.; Merrifield et al. (1963) J. Am. Chem. Soc.,85: 2149-2156, and Stewart et al. (1984) Solid Phase Peptide Synthesis,2nd ed. Pierce Chem. Co., Rockford, Ill.

In one embodiment, the peptides can be synthesized by the solid phasepeptide synthesis procedure using a benzhyderylamine resin (BeckmanBioproducts, 0.59 mmol of NH₂/g of resin) as the solid support. The COOHterminal amino acid (e.g., t-butylcarbonyl-Phe) is attached to the solidsupport through a 4-(oxymethyl)phenacetyl group. This is a more stablelinkage than the conventional benzyl ester linkage, yet the finishedpeptide can still be cleaved by hydrogenation. Transfer hydrogenationusing formic acid as the hydrogen donor can be used for this purpose.

It is noted that in the chemical synthesis of peptides, particularlypeptides comprising D amino acids, the synthesis usually produces anumber of truncated peptides in addition to the desired full-lengthproduct. Thus, the peptides are typically purified using, e.g., HPLC.

D-amino acids, beta amino acids, non-natural amino acids, and the likecan be incorporated at one or more positions in the peptide simply byusing the appropriately derivatized amino acid residue in the chemicalsynthesis. Modified residues for solid phase peptide synthesis arecommercially available from a number of suppliers (see, e.g., AdvancedChem Tech, Louisville; Nova Biochem, San Diego; Sigma, St Louis; BachemCalifornia Inc., Torrance, etc.). The D-form and/or otherwise modifiedamino acids can be completely omitted or incorporated at any position inthe peptide as desired. Thus, for example, in certain embodiments, thepeptide can comprise a single modified acid, while in other embodiments,the peptide comprises at least two, generally at least three, moregenerally at least four, most generally at least five, preferably atleast six, more preferably at least seven or even all modified aminoacids. In certain embodiments, essentially every amino acid is a D-formamino acid.

As indicated above, the peptides and/or fusion proteins of thisinvention can also be recombinantly expressed. Accordingly, in certainembodiments, the antimicrobial peptides and/or targeting moieties,and/or fusion proteins of this invention are synthesized usingrecombinant expression systems. Generally this involves creating a DNAsequence that encodes the desired peptide or fusion protein, placing theDNA in an expression cassette under the control of a particularpromoter, expressing the peptide or fusion protein in a host, isolatingthe expressed peptide or fusion protein and, if required, renaturing thepeptide or fusion protein.

DNA encoding the peptide(s) or fusion protein(s) described herein can beprepared by any suitable method as described above, including, forexample, cloning and restriction of appropriate sequences or directchemical synthesis.

This nucleic acid can be easily ligated into an appropriate vectorcontaining appropriate expression control sequences (e.g. promoter,enhancer, etc.), and, optionally, containing one or more selectablemarkers (e.g. antibiotic resistance genes).

The nucleic acid sequences encoding the peptides or fusion proteinsdescribed herein can be expressed in a variety of host cells, including,but not limited to, E. coli, other bacterial hosts, yeast, fungus, andvarious higher eukaryotic cells such as insect cells (e.g. SF3), theCOS, CHO and HeLa cells lines and myeloma cell lines. The recombinantprotein gene will typically be operably linked to appropriate expressioncontrol sequences for each host. For E. coli this can include a promotersuch as the T7, tip, or lambda promoters, a ribosome binding site andpreferably a transcription termination signal. For eukaryotic cells, thecontrol sequences can include a promoter and often an enhancer (e.g., anenhancer derived from immunoglobulin genes, SV40, cytomegalovirus,etc.), and a polyadenylation sequence, and may include splice donor andacceptor sequences.

The plasmids can be transferred into the chosen host cell by well-knownmethods such as calcium chloride transformation for E. coli and calciumphosphate treatment or electroporation for mammalian cells. Cellstransformed by the plasmids can be selected by resistance to antibioticsconferred by genes contained on the plasmids, such as the amp, gpt, neoand hyg genes.

Once expressed, the recombinant peptide(s) or fusion protein(s) can bepurified according to standard procedures of the art, including ammoniumsulfate precipitation, affinity columns, column chromatography, gelelectrophoresis and the like (see, generally, R. Scopes, (1982) ProteinPurification, Springer-Verlag, N.Y.; Deutscher (1990) Methods inEnzymology Vol. 182: Guide to Protein Purification., Academic Press,Inc. N.Y.). Substantially pure compositions of at least about 90 to 95%homogeneity are preferred, and 98 to 99% or more homogeneity are mostpreferred.

One of skill in the art would recognize that after chemical synthesis,biological expression, or purification, the peptide(s) or fusionprotein(s) may possess a conformation substantially different thandesired native conformation. In this case, it may be necessary todenature and reduce the peptide or fusion protein and then to cause themolecule to re-fold into the preferred conformation. Methods of reducingand denaturing proteins and inducing re-folding are well known to thoseof skill in the art (see, e.g., Debinski et al. (1993) J. Biol. Chem.,268: 14065-14070; Kreitman and Pastan (1993) Bioconjug. Chem., 4:581-585; and Buchner, et al., (1992) Anal. Biochem., 205: 263-270).Debinski et al., for example, describes the denaturation and reductionof inclusion body proteins in guanidine-DTE. The protein is thenrefolded in a redox buffer containing oxidized glutathione andL-arginine.

One of skill would recognize that modifications can be made to thepeptide(s) and/or fusion protein(s) proteins without diminishing theirbiological activity. Some modifications may be made to facilitate thecloning, expression, or incorporation of the targeting molecule into afusion protein. Such modifications are well known to those of skill inthe art and include, for example, a methionine added at the aminoterminus to provide an initiation site, or additional amino acids (e.g.,poly His) placed on either terminus to create conveniently locatedrestriction sites or termination codons or purification sequences.

D) Joining Targeting Moieties to Effectors.

i. Chemical Conjugation.

Chimeric moieties are formed by joining one or more of the targetingmoieties described herein to one or more effectors. In certainembodiments the targeting moieties are attached directly to theeffector(s) via naturally occurring reactive groups or the targetingmoiety and/or the effector(s) can be functionalized to provide suchreactive groups.

In various embodiments the targeting moieties are attached toeffector(s) via one or more linking agents. Thus, in various embodimentsthe targeting moieties and the effector(s) can be conjugated via asingle linking agent or multiple linking agents. For example, thetargeting moiety and the effector can be conjugated via a singlemultifunctional (e.g., bi-, tri-, or tetra-) linking agent or a pair ofcomplementary linking agents. In another embodiment, the targetingmoiety and the effector are conjugated via two, three, or more linkingagents. Suitable linking agents include, but are not limited to, e.g.,functional groups, affinity agents, stabilizing groups, and combinationsthereof.

In certain embodiments the linking agent is or comprises a functionalgroup. Functional groups include monofunctional linkers comprising areactive group as well as multifunctional crosslinkers comprising two ormore reactive groups capable of forming a bond with two or moredifferent functional targets (e.g., labels, proteins, macromolecules,semiconductor nanocrystals, or substrate). In some preferredembodiments, the multifunctional crosslinkers are heterobifunctionalcrosslinkers comprising two or more different reactive groups.

Suitable reactive groups include, but are not limited to thiol (—SH),carboxylate (COOH), carboxyl (—COOH), carbonyl, amine (NH₂), hydroxyl(—OH), aldehyde (—CHO), alcohol (ROH), ketone (R₂CO), active hydrogen,ester, sulfhydryl (SH), phosphate (—PO₃), or photoreactive moieties.Amine reactive groups include, but are not limited to e.g.,isothiocyanates, isocyanates, acyl azides, NHS esters, sulfonylchlorides, aldehydes and glyoxals, epoxides and oxiranes, carbonates,arylating agents, imidoesters, carbodiimides, and anhydrides.Thiol-reactive groups include, but are not limited to e.g., haloacetyland alkyl halide derivates, maleimides, aziridines, acryloylderivatives, arylating agents, and thiol-disulfides exchange reagents.Carboxylate reactive groups include, but are not limited to e.g.,diazoalkanes and diazoacetyl compounds, such as carbonyldiimidazoles andcarbodiimides. Hydroxyl reactive groups include, but are not limited toe.g., epoxides and oxiranes, carbonyldiimidazole, oxidation withperiodate, N,N′-disuccinimidyl carbonate or N-hydroxylsuccimidylchloroformate, enzymatic oxidation, alkyl halogens, and isocyanates.Aldehyde and ketone reactive groups include, but are not limited toe.g., hydrazine derivatives for schiff base formation or reductionamination. Active hydrogen reactive groups include, but are not limitedto e.g., diazonium derivatives for mannich condensation and iodinationreactions. Photoreactive groups include, but are not limited to e.g.,aryl azides and halogenated aryl azides, benzophenones, diazo compounds,and diazirine derivatives.

Other suitable reactive groups and classes of reactions useful informing chimeric moieties include those that are well known in the artof bioconjugate chemistry. Currently favored classes of reactionsavailable with reactive chelates are those which proceed underrelatively mild conditions. These include, but are not limited to,nucleophilic substitutions (e.g., reactions of amines and alcohols withacyl halides, active esters), electrophilic substitutions (e.g., enaminereactions), and additions to carbon-carbon and carbon-heteroatommultiple bonds (e.g., Michael reaction, Diels-Alder addition). These andother useful reactions are discussed in, for example, March (1985)Advanced Organic Chemistry, 3rd Ed., John Wiley & Sons, New York,Hermanson (1996) Bioconjugate Techniques, Academic Press, San Diego; andFeeney et al. (1982) Modification of Proteins; Advances in ChemistrySeries, Vol. 198, American Chemical Society, Washington, D.C.

In certain embodiments, the linking agent comprises a chelator. Forexample, the chelator comprising the molecule, DOTA(DOTA=1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane),can readily be labeled with a radiolabel, such as Gd³⁺ and ⁶⁴Cu,resulting in Gd³⁺-DOTA and ⁶⁴Cu-DOTA respectively, attached to thetargeting moiety. Other suitable chelates are known to those of skill inthe art, for example, 1,4,7-triazacyclononane-N,N′,N″-triacetic acid(NOTA) derivatives being among the most well known (see, e.g., Lee etal. (1997) Nucl Med. Biol. 24: 2225-23019).

A “linker” or “linking agent” as used herein, is a molecule that is usedto join two or more molecules. In certain embodiments the linker istypically capable of forming covalent bonds to both molecule(s) (e.g.,the targeting moiety and the effector). Suitable linkers are well knownto those of skill in the art and include, but are not limited to,straight or branched-chain carbon linkers, heterocyclic carbon linkers,or peptide linkers. In certain embodiments the linkers can be joined tothe constituent amino acids through their side groups (e.g., through adisulfide linkage to cysteine). However, in certain embodiments, thelinkers will be joined to the alpha carbon amino and carboxyl groups ofthe terminal amino acids.

A bifunctional linker having one functional group reactive with a groupon one molecule (e.g., a targeting peptide), and another group reactiveon the other molecule (e.g., an antimicrobial peptide), can be used toform the desired conjugate. Alternatively, derivatization can beperformed to provide functional groups. Thus, for example, proceduresfor the generation of free sulfhydryl groups on peptides are also known(See U.S. Pat. No. 4,659,839).

In certain embodiments the linking agent is a heterobifunctionalcrosslinker comprising two or more different reactive groups that form aheterocyclic ring that can interact with a peptide. For example, aheterobifunctional crosslinker such as cysteine may comprise an aminereactive group and a thiol-reactive group can interact with an aldehydeon a derivatized peptide. Additional combinations of reactive groupssuitable for heterobifunctional crosslinkers include, for example,amine- and sulfhydryl reactive groups; carbonyl and sulfhydryl reactivegroups; amine and photoreactive groups; sulfhydryl and photoreactivegroups; carbonyl and photoreactive groups; carboxylate and photoreactivegroups; and arginine and photoreactive groups. In one embodiment, theheterobifunctional crosslinker is SMCC.

Many procedures and linker molecules for attachment of various moleculesto peptides or proteins are known (see, e.g., European PatentApplication No. 188,256; U.S. Pat. Nos. 4,671,958, 4,659,839, 4,414,148,4,699,784; 4,680,338; 4,569,789; and 4,589,071; and Borlinghaus et al.(1987) Cancer Res. 47: 4071-4075). Illustrative linking protocols areprovided herein in Examples 2 and 3.

ii. Fusion Proteins.

In certain embodiments where the targeting moiety and effector are bothpeptides or both comprise peptides, the chimeric moiety can bechemically synthesized or recombinantly expressed as a fusion protein(i.e., a chimeric fusion protein).

In certain embodiments the chimeric fusion proteins are synthesizedusing recombinant DNA methodology. Generally this involves creating aDNA sequence that encodes the fusion protein, placing the DNA in anexpression cassette under the control of a particular promoter,expressing the protein in a host, isolating the expressed protein and,if required, renaturing the protein.

DNA encoding the fusion proteins can be prepared by any suitable method,including, for example, cloning and restriction of appropriate sequencesor direct chemical synthesis by methods such as the phosphotriestermethod of Narang et al. (1979) Meth. Enzymol. 68: 90-99; thephosphodiester method of Brown et al. (1979) Meth. Enzymol. 68: 109-151;the diethylphosphoramidite method of Beaucage et al. (1981) Tetra.Lett., 22: 1859-1862; and the solid support method of U.S. Pat. No.4,458,066.

Chemical synthesis produces a single stranded oligonucleotide. This canbe converted into double stranded DNA by hybridization with acomplementary sequence or by polymerization with a DNA polymerase usingthe single strand as a template. One of skill would recognize that whilechemical synthesis of DNA is limited to sequences of about 100 bases,longer sequences can be obtained by the ligation of shorter sequences.

Alternatively, subsequences can be cloned and the appropriatesubsequences cleaved using appropriate restriction enzymes. Thefragments can then be ligated to produce the desired DNA sequence.

In certain embodiments, DNA encoding fusion proteins of the presentinvention may be cloned using DNA amplification methods such aspolymerase chain reaction (PCR). Thus, for example, the nucleic acidencoding a targeting antibody, a targeting peptide, and the like is PCRamplified, using a sense primer containing the restriction site for NdeIand an antisense primer containing the restriction site for HindIII.This produces a nucleic acid encoding the targeting sequence and havingterminal restriction sites. Similarly an effector and/oreffector/linker/spacer can be provided having complementary restrictionsites. Ligation of sequences and insertion into a vector produces avector encoding the fusion protein.

While the targeting moieties and effector(s) can be directly joinedtogether, one of skill will appreciate that they can be separated by apeptide spacer/linker consisting of one or more amino acids. Generallythe spacer will have no specific biological activity other than to jointhe proteins or to preserve some minimum distance or other spatialrelationship between them. However, the constituent amino acids of thespacer may be selected to influence some property of the molecule suchas the folding, net charge, or hydrophobicity.

The nucleic acid sequences encoding the fusion proteins can be expressedin a variety of host cells, including E. coli, other bacterial hosts,yeast, and various higher eukaryotic cells such as the COS, CHO and HeLacells lines and myeloma cell lines. The recombinant protein gene will beoperably linked to appropriate expression control sequences for eachhost. For E. coli this includes a promoter such as the T7, tip, orlambda promoters, a ribosome binding site and preferably a transcriptiontermination signal. For eukaryotic cells, the control sequences willinclude a promoter and preferably an enhancer derived fromimmunoglobulin genes, SV40, cytomegalovirus, etc., and a polyadenylationsequence, and may include splice donor and acceptor sequences.

The plasmids can be transferred into the chosen host cell by well-knownmethods such as calcium chloride transformation for E. coli and calciumphosphate treatment or electroporation for mammalian cells. Cellstransformed by the plasmids can be selected by resistance to antibioticsconferred by genes contained on the plasmids, such as the amp, gpt, neoand hyg genes.

Once expressed, the recombinant fusion proteins can be purifiedaccording to standard procedures of the art, including ammonium sulfateprecipitation, affinity columns, column chromatography, gelelectrophoresis and the like (see, generally, R. Scopes (1982) ProteinPurification, Springer-Verlag, N.Y.; Deutscher (1990) Methods inEnzymology Vol. 182: Guide to Protein Purification., Academic Press,Inc. N.Y.). Substantially pure compositions of at least about 90 to 95%homogeneity are preferred, and 98 to 99% or more homogeneity are mostpreferred for pharmaceutical uses. Once purified, partially or tohomogeneity as desired, the polypeptides may then be usedtherapeutically.

One of skill in the art would recognize that after chemical synthesis,biological expression, or purification, the fusion protein may possess aconformation substantially different than the native conformations ofthe constituent polypeptides. In this case, it may be necessary todenature and reduce the polypeptide and then to cause the polypeptide tore-fold into the preferred conformation. Methods of reducing anddenaturing proteins and inducing re-folding are well known to those ofskill in the art (See, Debinski et al. (1993) J. Biol. Chem., 268:14065-14070; Kreitman and Pastan (1993) Bioconjug. Chem., 4: 581-585;and Buchner, et al. (1992) Anal. Biochem., 205: 263-270).

One of skill would recognize that modifications can be made to thefusion proteins without diminishing their biological activity. Somemodifications may be made to facilitate the cloning, expression, orincorporation of the targeting molecule into a fusion protein. Suchmodifications are well known to those of skill in the art and include,for example, a methionine added at the amino terminus to provide aninitiation site, or additional amino acids placed on either terminus tocreate conveniently located restriction sites or termination codons.

As indicated above, in various embodiments a peptide linker/spacer isused to join the one or more targeting moieties to one or moreeffector(s). In various embodiments the peptide linker is relativelyshort, typically less than about 10 amino acids, preferably less thanabout 8 amino acids and more preferably about 3 to about 5 amino acids.Suitable illustrative linkers include, but are not limited to PSGSP((SEQ ID NO:3209), ASASA (SEQ ID NO: 3210), or GGG. In certainembodiments longer linkers such as (GGGGS)₃ (SEQ ID NO:3211) can beused. Illustrative peptide linkers and other linkers are shown in Table16.

TABLE 16 Illustrative peptide and non-peptide linkers. Linker SEQ ID NO:AAA GGG GGGG 3212 SGG GGSGGS 3213 SAT PYP PSPSP 3214 ASA ASASA 3215PSPSP 3216 KKKK 3217 RRRR 3218 GGGGS 3219 GGGGS GGGGS 3220 GGGGS GGGGSGGGGS 3221 GGGGS GGGGS GGGGS GGGGS 3222 GGGGS GGGGS GGGGS GGGGS GGGGS3223 GGGGS GGGGS GGGGS GGGGS GGGGS GGGGS 3224 2-nitrobenzene orO-nitrobenzyl Nitropyridyl disulfide Dioleoylphosphatidylethanolamine(DOPE) S-acetylmercaptosuccinic acid1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracetic acid (DOTA)β-glucuronide and β-glucuronide variants Poly(alkylacrylic acid)Benzene-based linkers (for example: 2,5-Bis(hexyloxy)-1,4-bis[2,5-bis(hexyloxy)-4-formyl-phenylenevinylene]benzene) and like moleculesDisulfide linkages Poly(amidoamine) or like dendrimers linking multipletarget and killing peptides in one molecule Carbon nanotubes Hydrazoneand hydrazone variant linkers PEG of any chain length Succinate,formate, acetate butyrate, other like organic acids Aldols, alcohols, orenols Peroxides alkane or alkene groups of any chain length One or moreporphyrin or dye molecules containing free amide and carboxylic acidgroups One or more DNA or RNA nucleotides, including polyamine andpolycarboxyl-containing variants Inulin, sucrose, glucose, or othersingle, di or polysaccharides Linoleic acid or other polyunsaturatedfatty acids Variants of any of the above linkers containing halogen orthiol groups (All amino-acid-based linkers could be L, D, combinationsof L and D forms, β-form, and the like)

E) Multiple Targeting Moieties and/or Effectors.

As indicated above, in certain embodiments, the chimeric moietiesdescribed herein comprise multiple targeting moieties attached to asingle effector or multiple effectors attached to a single targetingmoiety, or multiple targeting moieties attached to multiple effectors.

Where the chimeric construct is a fusion protein this is easilyaccomplished by providing multiple domains that are targeting domainsattached to one or more effector domains. FIG. 14 schematicallyillustrates a few, but not all, configurations. In various embodimentsthe multiple targeting domains and/or multiple effector domains can beattached to each other directly or can be separated by linkers (e.g.,amino acid or peptide linkers as described above).

When the chimeric construct is a chemical conjugate linear or branchedconfigurations (e.g., as illustrated in FIG. 14) are readily produced byusing branched or multifunctional linkers and/or a plurality ofdifferent linkers.

F) Protecting Groups.

While the various peptides (e.g., targeting peptides, antimicrobialpeptides, STAMPs) described herein may be shown with no protectinggroups, in certain embodiments they can bear one, two, three, four, ormore protecting groups. In various embodiments, the protecting groupscan be coupled to the C- and/or N-terminus of the peptide(s) and/or toone or more internal residues comprising the peptide(s) (e.g., one ormore R-groups on the constituent amino acids can be blocked). Thus, forexample, in certain embodiments, any of the peptides described hereincan bear, e.g., an acetyl group protecting the amino terminus and/or anamide group protecting the carboxyl terminus. One example of such aprotected peptide is the 1845L6-21 STAMP having the amino acid sequenceKFINGVLSQFVLERKPYPKLFKFLRKHLL* (SEQ ID NO:3225), where the asteriskindicates an amidated carboxyl terminus. Of course, this protectinggroup can be can be eliminated and/or substituted with anotherprotecting group as described herein.

Without being bound by a particular theory, it was discovered thataddition of a protecting group, particularly to the carboxyl and incertain embodiments the amino terminus can improve the stability andefficacy of the peptide.

A wide number of protecting groups are suitable for this purpose. Suchgroups include, but are not limited to acetyl, amide, and alkyl groupswith acetyl and alkyl groups being particularly preferred for N-terminalprotection and amide groups being preferred for carboxyl terminalprotection. In certain particularly preferred embodiments, theprotecting groups include, but are not limited to alkyl chains as infatty acids, propionyl, formyl, and others. Particularly preferredcarboxyl protecting groups include amides, esters, and ether-formingprotecting groups. In one preferred embodiment, an acetyl group is usedto protect the amino terminus and an amide group is used to protect thecarboxyl terminus. These blocking groups enhance the helix-formingtendencies of the peptides. Certain particularly preferred blockinggroups include alkyl groups of various lengths, e.g., groups having theformula: CH₃—(CH₂)_(n)—CO— where n ranges from about 1 to about 20,preferably from about 1 to about 16 or 18, more preferably from about 3to about 13, and most preferably from about 3 to about 10.

In certain embodiments, the protecting groups include, but are notlimited to alkyl chains as in fatty acids, propionyl, formyl, andothers. Particularly preferred carboxyl protecting groups includeamides, esters, and ether-forming protecting groups. In one embodiment,an acetyl group is used to protect the amino terminus and/or an aminogroup is used to protect the carboxyl terminus (i.e., amidated carboxylterminus). In certain embodiments blocking groups include alkyl groupsof various lengths, e.g., groups having the formula: CH₃—(CH₂)_(n)—CO—where n ranges from about 3 to about 20, preferably from about 3 toabout 16, more preferably from about 3 to about 13, and most preferablyfrom about 3 to about 10.

In certain embodiments, the acid group on the C-terminal can be blockedwith an alcohol, aldehyde or ketone group and/or the N-terminal residuecan have the natural amide group, or be blocked with an acyl, carboxylicacid, alcohol, aldehyde, or ketone group.

Other protecting groups include, but are not limited to Fmoc,t-butoxycarbonyl (t-BOC), 9-fluoreneacetyl group, 1-fluorenecarboxylicgroup, 9-florenecarboxylic group, 9-fluorenone-1-carboxylic group,benzyloxycarbonyl, xanthyl (Xan), trityl (Trt), 4-methyltrityl (Mtt),4-methoxytrityl (Mmt), 4-methoxy-2,3,6-trimethyl-benzenesulphonyl (Mtr),Mesitylene-2-sulphonyl (Mts), 4,4-dimethoxybenzhydryl (Mbh), Tosyl(Tos), 2,2,5,7,8-pentamethyl chroman-6-sulphonyl (Pmc), 4-methylbenzyl(MeBzl), 4-methoxybenzyl (MeOBzl), benzyloxy (BzlO), benzyl (Bzl),benzoyl (Bz), 3-nitro-2-pyridinesulphenyl (Npys),1-(4,4-dimentyl-2,6-diaxocyclohexylidene)ethyl (Dde), 2,6-dichlorobenzyl(2,6-DiCl—Bzl), 2-chlorobenzyloxycarbonyl (2-Cl—Z),2-bromobenzyloxycarbonyl (2-Br—Z), Benzyloxymethyl (Bom), cyclohexyloxy(cHxO), t-butoxymethyl (Bum), t-butoxy (tBuO), t-Butyl (tBu), Acetyl(Ac), and Trifluoroacetyl (TFA).

Protecting/blocking groups are well known to those of skill as aremethods of coupling such groups to the appropriate residue(s) comprisingthe peptides of this invention (see, e.g., Greene et al., (1991)Protective Groups in Organic Synthesis, 2nd ed., John Wiley & Sons, Inc.Somerset, N.J.). In illustrative embodiment, for example, acetylation isaccomplished during the synthesis when the peptide is on the resin usingacetic anhydride. Amide protection can be achieved by the selection of aproper resin for the synthesis. For example, a rink amide resin can beused. After the completion of the synthesis, the semipermanentprotecting groups on acidic bifunctional amino acids such as Asp and Gluand basic amino acid Lys, hydroxyl of Tyr are all simultaneouslyremoved. The peptides released from such a resin using acidic treatmentcomes out with the n-terminal protected as acetyl and the carboxylprotected as NH₂ and with the simultaneous removal of all of the otherprotecting groups.

Where amino acid sequences are disclosed herein, amino acid sequencescomprising, one or more protecting groups, e.g., as described above (orany other commercially available protecting groups for amino acids used,e.g., in boc or fmoc peptide synthesis) are also contemplated.

G) Peptide Circularization.

In certain embodiments the peptides described herein (e.g., AMPs,compound AMPs, STAMPs, etc.) are circularized/cyclized to produce cyclicpeptides. Cyclic peptides, as contemplated herein, include head/tail,head/side chain, tail/side chain, and side chain/side chain cyclizedpeptides. In addition, peptides contemplated herein include homodet,containing only peptide bonds, and heterodet containing in additiondisulfide, ester, thioester-bonds, or other bonds.

The cyclic peptides can be prepared using virtually any art-knowntechnique for the preparation of cyclic peptides. For example, thepeptides can be prepared in linear or non-cyclized form usingconventional solution or solid phase peptide syntheses and cyclizedusing standard chemistries. Preferably, the chemistry used to cyclizethe peptide will be sufficiently mild so as to avoid substantiallydegrading the peptide. Suitable procedures for synthesizing the peptidesdescribed herein as well as suitable chemistries for cyclizing thepeptides are well known in the art.

In various embodiments cyclization can be achieved via direct couplingof the N- and C-terminus to form a peptide (or other) bond, but can alsooccur via the amino acid side chains. Furthermore it can be based on theuse of other functional groups, including but not limited to amino,hydroxy, sulfhydryl, halogen, sulfonyl, carboxy, and thiocarboxy. Thesegroups can be located at the amino acid side chains or be attached totheir N- or C-terminus.

Accordingly, it is to be understood that the chemical linkage used tocovalently cyclize the peptides of the invention need not be an amidelinkage. In many instances it may be desirable to modify the N- andC-termini of the linear or non-cyclized peptide so as to provide, forexample, reactive groups that may be cyclized under mild reactionconditions. Such linkages include, by way of example and not limitationamide, ester, thioester, CH₂—NH, etc. Techniques and reagents forsynthesizing peptides having modified termini and chemistries suitablefor cyclizing such modified peptides are well-known in the art.

Alternatively, in instances where the ends of the peptide areconformationally or otherwise constrained so as to make cyclizationdifficult, it may be desirable to attach linkers to the N- and/orC-termini to facilitate peptide cyclization. Of course, it will beappreciated that such linkers will bear reactive groups capable offorming covalent bonds with the termini of the peptide. Suitable linkersand chemistries are well-known in the art and include those previouslydescribed.

Cyclic peptides and depsipeptides (heterodetic peptides that includeester (depside) bonds as part of their backbone) have been wellcharacterized and show a wide spectrum of biological activity. Thereduction in conformational freedom brought about by cyclization oftenresults in higher receptor-binding affinities. Frequently in thesecyclic compounds, extra conformational restrictions are also built in,such as the use of D- and N-alkylated-amino acids, α,β-dehydro aminoacids or α,α-disubstituted amino acid residues.

Methods of forming disulfide linkages in peptides are well known tothose of skill in the art (see, e.g., Eichler and Houghten (1997)Protein Pept. Lett. 4: 157-164).

Reference may also be made to Marlowe (1993) Biorg. Med. Chem. Lett. 3:437-44 who describes peptide cyclization on TFA resin usingtrimethylsilyl (TMSE) ester as an orthogonal protecting group; Pallinand Tam (1995) J. Chem. Soc. Chem. Comm. 2021-2022) who describe thecyclization of unprotected peptides in aqueous solution by oximeformation; Algin et al. (1994) Tetrahedron Lett. 35: 9633-9636 whodisclose solid-phase synthesis of head-to-tail cyclic peptides vialysine side-chain anchoring; Kates et al. (1993) Tetrahedron Lett. 34:1549-1552 who describe the production of head-to-tail cyclic peptides bythree-dimensional solid phase strategy; Tumelty et al. (1994) J. Chem.Soc. Chem. Comm. 1067-1068, who describe the synthesis of cyclicpeptides from an immobilized activated intermediate, where activation ofthe immobilized peptide is carried out with N-protecting group intactand subsequent removal leading to cyclization; McMurray et al. (1994)Peptide Res. 7: 195-206) who disclose head-to-tail cyclization ofpeptides attached to insoluble supports by means of the side chains ofaspartic and glutamic acid; Hruby et al. (1994) Reactive Polymers 22:231-241) who teach an alternate method for cyclizing peptides via solidsupports; and Schmidt and Langer (1997) J. Peptide Res. 49: 67-73, whodisclose a method for synthesizing cyclotetrapeptides andcyclopentapeptides.

These methods of peptide cyclization are illustrative and non-limiting.Using the teaching provide herein, other cyclization methods will beavailable to one of skill in the art.

H) Identification/Verification of Active Peptides

The active AMPs, STAMPs and the like can be identified and/or validatedusing an in vitro screening assay. Indeed, in many instances the AMPsand/or STAMPS described herein will be used in vitro as preservatives,topical antimicrobial treatments, and the like. Additionally, despitecertain apparent limitations of in vitro susceptibility tests, clinicaldata indicate that a good correlation exists between minimal inhibitoryconcentration (MIC) test results and in vivo efficacy of antibioticcompounds (see, e.g., Murray et al. (1994) Antimicrobial SusceptibilityTesting, Poupard et al., eds., Plenum Press, New York; Knudsen et al.(1995) Antimicrob. Agents Chemother. 39(6): 1253-1258; and the like).Thus, AMPs useful for treating infections and diseases related theretoare also conveniently identified by demonstrated in vitro antimicrobialactivity against specified microbial targets, e.g., as illustrated inTable 4).

Typically, the in vitro antimicrobial activity of antimicrobial agentsis tested using standard NCCLS bacterial inhibition assays, or MIC tests(see, National Committee on Clinical Laboratory Standards “PerformanceStandards for Antimicrobial Susceptibility Testing,” NCCLS DocumentM100-S5 Vol. 14, No. 16, December 1994; “Methods for dilutionantimicrobial susceptibility test for bacteria that growaerobically-Third Edition,” Approved Standard M7-A3, National Committeefor Clinical Standards, Villanova, Pa.).

It will be appreciated that other assays as are well known in the art orthat will become apparent to those having skill in the art upon reviewof this disclosure may also be used to identify active AMPs. Such assaysinclude, for example, the assay described in Lehrer et al. (1988) J.Immunol. Meth., 108: 153 and Steinberg and Lehrer, “Designer Assays forAntimicrobial Peptides: Disputing the ‘One Size Fits All’ Theory,” In:Antibacterial Peptide Protocols, Shafer, Ed., Humana Press, N.J.Generally, active peptides of the invention will exhibit MICs (asmeasured using the assays described in the examples) of less than about100 μM, preferably less than about 80 or 60 μM, more preferably about 50μM or less, about 25 μM or less, or about 15 μM or less, or about 10 μMor less.

IV. Administration and Formulations.

A) Pharmaceutical Formulations.

In certain embodiments, the antimicrobial peptides and/or the chimericconstructs (e.g., targeting moieties attached to antimicrobialpeptide(s), targeting moieties attached to detectable label(s), etc.)are administered to a mammal in need thereof, to a cell, to a tissue, toa composition (e.g., a food), etc.). In various embodiments thecompositions can be administered to detect and/or locate, and/orquantify the presence of particular microorganisms, microorganismpopulations, biofilms comprising particular microorganisms, and thelike. In various embodiments the compositions can be administered toinhibit particular microorganisms, microorganism populations, biofilmscomprising particular microorganisms, and the like.

These active agents (antimicrobial peptides and/or chimeric moieties)can be administered in the “native” form or, if desired, in the form ofsalts, esters, amides, prodrugs, derivatives, and the like, provided thesalt, ester, amide, prodrug or derivative is suitable pharmacologically,i.e., effective in the present method(s). Salts, esters, amides,prodrugs and other derivatives of the active agents can be preparedusing standard procedures known to those skilled in the art of syntheticorganic chemistry and described, for example, by March (1992) AdvancedOrganic Chemistry; Reactions, Mechanisms and Structure, 4th Ed. N.Y.Wiley-Interscience.

Methods of formulating such derivatives are known to those of skill inthe art. For example, the disulfide salts of a number of delivery agentsare described in PCT Publication WO 2000/059863 which is incorporatedherein by reference. Similarly, acid salts of therapeutic peptides,peptoids, or other mimetics, and can be prepared from the free baseusing conventional methodology that typically involves reaction with asuitable acid. Generally, the base form of the drug is dissolved in apolar organic solvent such as methanol or ethanol and the acid is addedthereto. The resulting salt either precipitates or can be brought out ofsolution by addition of a less polar solvent. Suitable acids forpreparing acid addition salts include, but are not limited to bothorganic acids, e.g., acetic acid, propionic acid, glycolic acid, pyruvicacid, oxalic acid, malic acid, malonic acid, succinic acid, maleic acid,fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid,mandelic acid, methanesulfonic acid, ethanesulfonic acid,p-toluenesulfonic acid, salicylic acid, and the like, as well asinorganic acids, e.g., hydrochloric acid, hydrobromic acid, sulfuricacid, nitric acid, phosphoric acid, and the like. An acid addition saltcan be reconverted to the free base by treatment with a suitable base.Certain particularly preferred acid addition salts of the active agentsherein include halide salts, such as may be prepared using hydrochloricor hydrobromic acids. Conversely, preparation of basic salts of theactive agents of this invention are prepared in a similar manner using apharmaceutically acceptable base such as sodium hydroxide, potassiumhydroxide, ammonium hydroxide, calcium hydroxide, trimethylamine, or thelike. In certain embodiments basic salts include alkali metal salts,e.g., the sodium salt, and copper salts.

For the preparation of salt forms of basic drugs, the pKa of thecounterion is preferably at least about 2 pH lower than the pKa of thedrug. Similarly, for the preparation of salt forms of acidic drugs, thepKa of the counterion is preferably at least about 2 pH higher than thepKa of the drug. This permists the counterion to bring the solution's pHto a level lower than the pHmax to reach the salt plateau, at which thesolubility of salt prevails over the solubility of free acid or base.The generalized rule of difference in pKa units of the ionizable groupin the active pharmaceutical ingredient (API) and in the acid or base ismeant to make the proton transfer energetically favorable. When the pKaof the API and counterion are not significantly different, a solidcomplex may form but may rapidly disproportionate (i.e., break down intothe individual entities of drug and counterion) in an aqueousenvironment.

Preferably, the counterion is a pharmaceutically acceptable counterion.Suitable anionic salt forms include, but are not limited to acetate,benzoate, benzylate, bitartrate, bromide, carbonate, chloride, citrate,edetate, edisylate, estolate, fumarate, gluceptate, gluconate,hydrobromide, hydrochloride, iodide, lactate, lactobionate, malate,maleate, mandelate, mesylate, methyl bromide, methyl sulfate, mucate,napsylate, nitrate, pamoate (embonate), phosphate and diphosphate,salicylate and disalicylate, stearate, succinate, sulfate, tartrate,tosylate, triethiodide, valerate, and the like, while suitable cationicsalt forms include, but are not limited to aluminum, benzathine,calcium, ethylene diamine, lysine, magnesium, meglumine, potassium,procaine, sodium, tromethamine, zinc, and the like.

In various embodiments preparation of esters typically involvesfunctionalization of hydroxyl and/or carboxyl groups that are presentwithin the molecular structure of the active agent. In certainembodiments, the esters are typically acyl-substituted derivatives offree alcohol groups, i.e., moieties that are derived from carboxylicacids of the formula RCOOH where R is alky, and preferably is loweralkyl. Esters can be reconverted to the free acids, if desired, by usingconventional hydrogenolysis or hydrolysis procedures.

Amides can also be prepared using techniques known to those skilled inthe art or described in the pertinent literature. For example, amidesmay be prepared from esters, using suitable amine reactants, or they maybe prepared from an anhydride or an acid chloride by reaction withammonia or a lower alkyl amine.

In various embodiments, the active agents identified herein are usefulfor parenteral, topical, oral, nasal (or otherwise inhaled), rectal, orlocal administration, such as by aerosol or transdermally, for detectionand/or quantification, and or localization, and/or prophylactic and/ortherapeutic treatment of infection (e.g., microbial infection). Thecompositions can be administered in a variety of unit dosage formsdepending upon the method of administration. Suitable unit dosage forms,include, but are not limited to powders, tablets, pills, capsules,lozenges, suppositories, patches, nasal sprays, injectibles, implantablesustained-release formulations, lipid complexes, etc.

The active agents (e.g., antimicrobial peptides and/or chimericconstructs) described herein can also be combined with apharmaceutically acceptable carrier (excipient) to form apharmacological composition. In certain embodiments, pharmaceuticallyacceptable carriers include those approved by a regulatory agency of theFederal or a state government or listed in the U.S. Pharmacopeia orother generally recognized pharmacopeia for use in/on animals, and moreparticularly in/on humans. A “carrier” refers to, for example, adiluent, adjuvant, excipient, auxiliary agent or vehicle with which anactive agent of the present invention is administered.

Pharmaceutically acceptable carriers can contain one or morephysiologically acceptable compound(s) that act, for example, tostabilize the composition or to increase or decrease the absorption ofthe active agent(s). Physiologically acceptable compounds can include,for example, carbohydrates, such as glucose, sucrose, or dextrans,antioxidants, such as ascorbic acid or glutathione, chelating agents,low molecular weight proteins, protection and uptake enhancers such aslipids, compositions that reduce the clearance or hydrolysis of theactive agents, or excipients or other stabilizers and/or buffers.

Other physiologically acceptable compounds, particularly of use in thepreparation of tablets, capsules, gel caps, and the like include, butare not limited to binders, diluent/fillers, disentegrants, lubricants,suspending agents, and the like.

In certain embodiments, to manufacture an oral dosage form (e.g., atablet), an excipient (e.g., lactose, sucrose, starch, mannitol, etc.),an optional disintegrator (e.g. calcium carbonate,carboxymethylcellulose calcium, sodium starch glycollate, crospovidoneetc.), a binder (e.g. alpha-starch, gum arabic, microcrystallinecellulose, carboxymethylcellulose, polyvinylpyrrolidone,hydroxypropylcellulose, cyclodextrin, etc.), and an optional lubricant(e.g., talc, magnesium stearate, polyethylene glycol 6000, etc.), forinstance, are added to the active component or components (e.g., activepeptide) and the resulting composition is compressed. Where necessarythe compressed product is coated, e.g., known methods for masking thetaste or for enteric dissolution or sustained release. Suitable coatingmaterials include, but are not limited to ethyl-cellulose,hydroxymethylcellulose, polyoxyethylene glycol, cellulose acetatephthalate, hydroxypropylmethylcellulose phthalate, and Eudragit (Rohm &Haas, Germany; methacrylic-acrylic copolymer).

Other physiologically acceptable compounds include wetting agents,emulsifying agents, dispersing agents or preservatives that areparticularly useful for preventing the growth or action ofmicroorganisms. Various preservatives are well known and include, forexample, phenol and ascorbic acid. One skilled in the art wouldappreciate that the choice of pharmaceutically acceptable carrier(s),including a physiologically acceptable compound depends, for example, onthe route of administration of the active agent(s) and on the particularphysio-chemical characteristics of the active agent(s).

In certain embodiments the excipients are sterile and generally free ofundesirable matter. These compositions can be sterilized byconventional, well-known sterilization techniques. For various oraldosage form excipients such as tablets and capsules sterility is notrequired. The USP/NF standard is usually sufficient.

In certain therapeutic applications, the compositions of this inventionare administered, e.g., topically administered or administered to theoral or nasal cavity, to a patient suffering from infection or at riskfor infection or prophylactically to prevent dental caries or otherpathologies of the teeth or oral mucosa characterized by microbialinfection in an amount sufficient to prevent and/or cure and/or at leastpartially prevent or arrest the disease and/or its complications. Anamount adequate to accomplish this is defined as a “therapeuticallyeffective dose.” Amounts effective for this use will depend upon theseverity of the disease and the general state of the patient's health.Single or multiple administrations of the compositions may beadministered depending on the dosage and frequency as required andtolerated by the patient. In any event, the composition should provide asufficient quantity of the active agents of the formulations of thisinvention to effectively treat (ameliorate one or more symptoms in) thepatient.

The concentration of active agent(s) can vary widely, and will beselected primarily based on activity of the active ingredient(s), bodyweight and the like in accordance with the particular mode ofadministration selected and the patient's needs. Concentrations,however, will typically be selected to provide dosages ranging fromabout 0.1 or 1 mg/kg/day to about 50 mg/kg/day and sometimes higher.Typical dosages range from about 3 mg/kg/day to about 3.5 mg/kg/day,preferably from about 3.5 mg/kg/day to about 7.2 mg/kg/day, morepreferably from about 7.2 mg/kg/day to about 11.0 mg/kg/day, and mostpreferably from about 11.0 mg/kg/day to about 15.0 mg/kg/day. In certainpreferred embodiments, dosages range from about 10 mg/kg/day to about 50mg/kg/day. In certain embodiments, dosages range from about 20 mg toabout 50 mg given orally twice daily. It will be appreciated that suchdosages may be varied to optimize a therapeutic and/or phophylacticregimen in a particular subject or group of subjects.

In certain embodiments, the active agents of this invention areadministered to the oral cavity. This is readily accomplished by the useof lozenges, aersol sprays, mouthwash, coated swabs, and the like.

In certain embodiments, the active agent(s) of this invention areadministered topically, e.g., to the skin surface, to a topical lesionor wound, to a surgical site, and the like.

In certain embodiments the active agents of this invention areadministered systemically (e.g., orally, or as an injectable) inaccordance with standard methods well known to those of skill in theart. In other preferred embodiments, the agents, can also be deliveredthrough the skin using conventional transdermal drug delivery systems,i.e., transdermal “patches” wherein the active agent(s) are typicallycontained within a laminated structure that serves as a drug deliverydevice to be affixed to the skin. In such a structure, the drugcomposition is typically contained in a layer, or “reservoir,”underlying an upper backing layer. It will be appreciated that the term“reservoir” in this context refers to a quantity of “activeingredient(s)” that is ultimately available for delivery to the surfaceof the skin. Thus, for example, the “reservoir” may include the activeingredient(s) in an adhesive on a backing layer of the patch, or in anyof a variety of different matrix formulations known to those of skill inthe art. The patch may contain a single reservoir, or it may containmultiple reservoirs.

In one embodiment, the reservoir comprises a polymeric matrix of apharmaceutically acceptable contact adhesive material that serves toaffix the system to the skin during drug delivery. Examples of suitableskin contact adhesive materials include, but are not limited to,polyethylenes, polysiloxanes, polyisobutylenes, polyacrylates,polyurethanes, and the like. Alternatively, the drug-containingreservoir and skin contact adhesive are present as separate and distinctlayers, with the adhesive underlying the reservoir which, in this case,may be either a polymeric matrix as described above, or it may be aliquid or hydrogel reservoir, or may take some other form. The backinglayer in these laminates, which serves as the upper surface of thedevice, preferably functions as a primary structural element of the“patch” and provides the device with much of its flexibility. Thematerial selected for the backing layer is preferably substantiallyimpermeable to the active agent(s) and any other materials that arepresent.

Other formulations for topical delivery include, but are not limited to,ointments, gels, sprays, fluids, and creams. Ointments are semisolidpreparations that are typically based on petrolatum or other petroleumderivatives. Creams containing the selected active agent are typicallyviscous liquid or semisolid emulsions, often either oil-in-water orwater-in-oil. Cream bases are typically water-washable, and contain anoil phase, an emulsifier and an aqueous phase. The oil phase, alsosometimes called the “internal” phase, is generally comprised ofpetrolatum and a fatty alcohol such as cetyl or stearyl alcohol; theaqueous phase usually, although not necessarily, exceeds the oil phasein volume, and generally contains a humectant. The emulsifier in a creamformulation is generally a nonionic, anionic, cationic or amphotericsurfactant. The specific ointment or cream base to be used, as will beappreciated by those skilled in the art, is one that will provide foroptimum drug delivery. As with other carriers or vehicles, an ointmentbase should be inert, stable, nonirritating and nonsensitizing.

As indicated above, various buccal, and sublingual formulations are alsocontemplated.

In certain embodiments, one or more active agents of the presentinvention can be provided as a “concentrate”, e.g., in a storagecontainer (e.g., in a premeasured volume) ready for dilution, or in asoluble capsule ready for addition to a volume of water, alcohol,hydrogen peroxide, or other diluent.

While the invention is described with respect to use in humans, it isalso suitable for animal, e.g., veterinary use. Thus certain preferredorganisms include, but are not limited to humans, non-human primates,canines, equines, felines, porcines, ungulates, largomorphs, and thelike.

B) Nanoemulsion Formulations.

In certain embodiments the targeting peptides, antimicrobial peptidesand/or chimeric moieties (e.g., STAMPs) as described herein areformulated in a nanoemulsion. Nanoemulsions include, but are not limitedto oil in water (O/W) nanoemulsions, and water in oil (W/O)nanoemulsions. Nanoemulsions can be defined as emulsions with meandroplet diameters ranging from about 20 to about 1000 nm. Usually, theaverage droplet size is between about 20 nm or 50 nm and about 500 nm.The terms sub-micron emulsion (SME) and mini-emulsion are used assynonyms.

Illustrative oil in water (O/W) nanoemulsions include, but are notlimited to:

Surfactant micelles—micelles composed of small molecules surfactants ordetergents (e.g., SDS/PBS/2-propanol) which are suitable forpredominantly hydrophobic peptides.

Polymer micelles—micelles composed of polymer, copolymer, or blockcopolymer surfactants (e.g., Pluronic L64/PBS/2-propanol) which aresuitable for predominantly hydrophobic peptides;

Blended micelles: micelles in which there is more than one surfactantcomponent or in which one of the liquid phases (generally an alcohol orfatty acid compound) participates in the formation of the micelle (e.g.,Octanoic acid/PBS/EtOH) which are suitable for predominantly hydrophobicpeptides;

Integral peptide micelles—blended micelles in which the peptide servesas an auxiliary surfactant, forming an integral part of the micelle(e.g., amphipathic peptide/PBS/mineral oil) which are suitable foramphipathic peptides; and

Pickering (solid phase) emulsions—emulsions in which the peptides areassociated with the exterior of a solid nanoparticle (e.g., polystyrenenanoparticles/PBS/no oil phase) which are suitable for amphipathicpeptides.

Illustrative water in oil (W/O) nanoemulsions include, but are notlimited to:

Surfactant micelles—micelles composed of small molecules surfactants ordetergents (e.g., dioctyl sulfosuccinate/PBS/2-propanol,Isopropylmyristate/PBS/2-propanol, etc.) which are suitable forpredominantly hydrophilic peptides;

Polymer micelles—micelles composed of polymer, copolymer, or blockcopolymer surfactants (e.g., PLURONIC® L121/PBS/2-propanol), which aresuitable for predominantly hydrophilic peptides;

Blended micelles—micelles in which there is more than one surfactantcomponent or in which one of the liquid phases (generally an alcohol orfatty acid compound) participates in the formation of the micelle (e.g.,capric/caprylic diglyceride/PBS/EtOH) which are suitable forpredominantly hydrophilic peptides;

Integral peptide micelles—blended micelles in which the peptide servesas an auxiliary surfactant, forming an integral part of the micelle(e.g., amphipathic peptide/PBS/polypropylene glycol) which are suitablefor amphipathic peptides; and

Pickering (solid phase) emulsions—emulsions in which the peptides areassociated with the exterior of a solid nanoparticle (e.g., chitosannanoparticles/no aqueous phase/mineral oil) which are suitable foramphipathic peptides.

As indicated above, in certain embodiments the nanoemulsions compriseone or more surfactants or detergents. In some embodiments thesurfactant is a non-anionic detergent (e.g., a polysorbate surfactant, apolyoxyethylene ether, etc.). Surfactants that find use in the presentinvention include, but are not limited to surfactants such as theTWEEN®, TRITON®, and TYLOXAPOL® families of compounds.

In certain embodiments the emulsions further comprise one or morecationic halogen containing compounds, including but not limited to,cetylpyridinium chloride. In still further embodiments, the compositionsfurther comprise one or more compounds that increase the interaction(“interaction enhancers”) of the composition with microorganisms (e.g.,chelating agents like ethylenediaminetetraacetic acid, orethylenebis(oxyethylenenitrilo)tetraacetic acid in a buffer).

In some embodiments, the nanoemulsion further comprises an emulsifyingagent to aid in the formation of the emulsion. Emulsifying agentsinclude compounds that aggregate at the oil/water interface to form akind of continuous membrane that prevents direct contact between twoadjacent droplets. Certain embodiments of the present invention featureoil-in-water emulsion compositions that may readily be diluted withwater to a desired concentration without impairing their anti-pathogenicproperties.

In addition to discrete oil droplets dispersed in an aqueous phase,certain oil-in-water emulsions can also contain other lipid structures,such as small lipid vesicles (e.g., lipid spheres that often consist ofseveral substantially concentric lipid bilayers separated from eachother by layers of aqueous phase), micelles (e.g., amphiphilic moleculesin small clusters of 50-200 molecules arranged so that the polar headgroups face outward toward the aqueous phase and the apolar tails aresequestered inward away from the aqueous phase), or lamellar phases(lipid dispersions in which each particle consists of parallelamphiphilic bilayers separated by thin films of water).

These lipid structures are formed as a result of hydrophobic forces thatdrive apolar residues (e.g., long hydrocarbon chains) away from water.The above lipid preparations can generally be described as surfactantlipid preparations (SLPs). SLPs are minimally toxic to mucous membranesand are believed to be metabolized within the small intestine (see e.g.,Hamouda et al., (1998) J. Infect. Disease 180: 1939).

In certain embodiments the emulsion comprises a discontinuous oil phasedistributed in an aqueous phase, a first component comprising an alcoholand/or glycerol, and a second component comprising a surfactant or ahalogen-containing compound. The aqueous phase can comprise any type ofaqueous phase including, but not limited to, water (e.g., dionizedwater, distilled water, tap water) and solutions (e.g., phosphatebuffered saline solution, or other buffer systems). The oil phase cancomprise any type of oil including, but not limited to, plant oils(e.g., soybean oil, avocado oil, flaxseed oil, coconut oil, cottonseedoil, squalene oil, olive oil, canola oil, corn oil, rapeseed oil,safflower oil, and sunflower oil), animal oils (e.g., fish oil), flavoroil, water insoluble vitamins, mineral oil, and motor oil. In certainembodiments, the oil phase comprises 30-90 vol % of the oil-in-wateremulsion (i.e., constitutes 30-90% of the total volume of the finalemulsion), more preferably 50-80%.

In certain embodiments the alcohol, when present, is ethanol.

While the present invention is not limited by the nature of thesurfactant, in some preferred embodiments, the surfactant is apolysorbate surfactant (e.g., TWEEN 20®, TWEEN 40®, TWEEN 60®, and TWEEN80®), a pheoxypolyethoxyethanol (e.g., TRITON® X-100, X-301, X-165,X-102, and X-200, and TYLOXAPOL®), or sodium dodecyl sulfate, and thelike.

In certain embodiments a halogen-containing component is present. thenature of the halogen-containing compound, in some preferred embodimentsthe halogen-containing compound comprises a chloride salt (e.g., NaCl,KCl, etc.), a cetylpyridinium halide, a cetyltrimethylammonium halide, acetyldimethylethylammonium halide, a cetyldimethylbenzylammonium halide,a cetyltributylphosphonium halide, dodecyltrimethylammonium halides,tetradecyltrimethylammonium halides, cetylpyridinium chloride,cetyltrimethylammonium chloride, cetylbenzyldimethylammonium chloride,cetylpyridinium bromide, cetyltrimethylammonium bromide,cetyldimethylethylammonium bromide, cetyltributylphosphonium bromide,dodecyltrimethylammonium bromide, tetradecyltrimethylammonium bromide,and the like

In certain embodiments the emulsion comprises a quaternary ammoniumcompound. Quaternary ammonium compounds include, but are not limited to,N-alkyldimethyl benzyl ammonium saccharinate,1,3,5-Triazine-1,3,5(2H,4H,6H)-triethanol; 1-Decanaminium,N-decyl-N,N-dimethyl-, chloride (or) Didecyl dimethyl ammonium chloride;2-(2-(p-(Diisobuyl)cresosxy)ethoxy)ethyl dimethyl benzyl ammoniumchloride; 2-(2-(p-(Diisobutyl)phenoxy)ethoxy)ethyl dimethyl benzylammonium chloride; alkyl 1 or 3-benzyl-1-(2-hydroxethyl)-2-imidazoliniumchloride; alkyl bis(2-hydroxyethyl)benzyl ammonium chloride; alkyldemethyl benzyl ammonium chloride; alkyl dimethyl 3,4-dichlorobenzylammonium chloride (100% C12); alkyl dimethyl 3,4-dichlorobenzyl ammoniumchloride (50% C14, 40% C12, 10% C16); alkyl dimethyl 3,4-dichlorobenzylammonium chloride (55% C14, 23% C12, 20% C16); alkyl dimethyl benzylammonium chloride; alkyl dimethyl benzyl ammonium chloride (100% C14);alkyl dimethyl benzyl ammonium chloride (100% C16); alkyl dimethylbenzyl ammonium chloride (41% C14, 28% C12); alkyl dimethyl benzylammonium chloride (47% C12, 18% C14); alkyl dimethyl benzyl ammoniumchloride (55% C16, 20% C14); alkyl dimethyl benzyl ammonium chloride(58% C14, 28% C16); alkyl dimethyl benzyl ammonium chloride (60% C14,25% C12); alkyl dimethyl benzyl ammonium chloride (61% C11, 23% C14);alkyl dimethyl benzyl ammonium chloride (61% C12, 23% C14); alkyldimethyl benzyl ammonium chloride (65% C12, 25% C14); alkyl dimethylbenzyl ammonium chloride (67% C12, 24% C14); alkyl dimethyl benzylammonium chloride (67% C12, 25% C14); alkyl dimethyl benzyl ammoniumchloride (90% C14, 5% C12); alkyl dimethyl benzyl ammonium chloride (93%C14, 4% C12); alkyl dimethyl benzyl ammonium chloride (95% C16, 5% C18);alkyl dimethyl benzyl ammonium chloride (and) didecyl dimethyl ammoniumchloride; alkyl dimethyl benzyl ammonium chloride (as in fatty acids);alkyl dimethyl benzyl ammonium chloride (C12-C16); alkyl dimethyl benzylammonium chloride (C12-C18); alkyl dimethyl benzyl and dialkyl dimethylammonium chloride; alkyl dimethyl dimethybenzyl ammonium chloride; alkyldimethyl ethyl ammonium bromide (90% C14, 5% C16, 5% C12); alkyldimethyl ethyl ammonium bromide (mixed alkyl and alkenyl groups as inthe fatty acids of soybean oil); alkyl dimethyl ethylbenzyl ammoniumchloride; alkyl dimethyl ethylbenzyl ammonium chloride (60% C14); alkyldimethyl isoproylbenzyl ammonium chloride (50% C12, 30% C14, 17% C16, 3%C18); alkyl trimethyl ammonium chloride (58% C18, 40% C16, 1% C14, 1%C12); alkyl trimethyl ammonium chloride (90% C18, 10% C16);alkyldimethyl(ethylbenzyl) ammonium chloride (C12-18); Di-(C8-10)-alkyldimethyl ammonium chlorides; dialkyl dimethyl ammonium chloride; dialkyldimethyl ammonium chloride; dialkyl dimethyl ammonium chloride; dialkylmethyl benzyl ammonium chloride; didecyl dimethyl ammonium chloride;diisodecyl dimethyl ammonium chloride; dioctyl dimethyl ammoniumchloride; dodecyl bis(2-hydroxyethyl) octyl hydrogen ammonium chloride;dodecyl dimethyl benzyl ammonium chloride; dodecylcarbamoyl methyldimethyl benzyl ammonium chloride; heptadecyl hydroxyethylimidazoliniumchloride; hexahydro-1,3,5-thris(2-hydroxyethyl)-s-triazine;myristalkonium chloride (and) Quat RNIUM 14;N,N-Dimethyl-2-hydroxypropylammonium chloride polymer; n-alkyl dimethylbenzyl ammonium chloride; n-alkyl dimethyl ethylbenzyl ammoniumchloride; n-tetradecyl dimethyl benzyl ammonium chloride monohydrate;octyl decyl dimethyl ammonium chloride; octyl dodecyl dimethyl ammoniumchloride; octyphenoxyethoxyethyl dimethyl benzyl ammonium chloride;oxydiethylenebis (alkyl dimethyl ammonium chloride); quaternary ammoniumcompounds, dicoco alkyldimethyl, chloride; trimethoxysily propyldimethyl octadecyl ammonium chloride; trimethoxysilyl quats, trimethyldodecylbenzyl ammonium chloride; n-dodecyl dimethyl ethylbenzyl ammoniumchloride; n-hexadecyl dimethyl benzyl ammonium chloride; n-tetradecyldimethyl benzyl ammonium chloride; n-tetradecyl dimethyl ethylbenzylammonium chloride; and n-octadecyl dimethyl benzyl ammonium chloride.

Nanoemulsion formulations and methods of making such are well known tothose of skill in the art and described for example in U.S. Pat. Nos.7,476,393, 7,468,402, 7,314,624, 6,998,426, 6,902,737, 6,689,371,6,541,018, 6,464,990, 6,461,625, 6,419,946, 6,413,527, 6,375,960,6,335,022, 6,274,150, 6,120,778, 6,039,936, 5,925,341, 5,753,241,5,698,219, and 5,152,923 and in Fanun et al. (2009) Microemulsions:Properties and Applications (Surfactant Science), CRC Press, Boca RatanFl.

C) Formulations Optimizing Activity.

In certain embodiments, formulations are selected to optimize bindingspecificity, and/or binding avidity, and/or antimicrobial activity,and/or stability/conformation of the targeting peptide, antimicrobialpeptide, chimeric moiety, and/or STAMP. In this regard, it was asurprising discovery that the activity of certain STAMPs, and presumablythe constituent targeting peptides and/or antimicrobial peptides wasoptimized in the presence of a salt. Accordingly, certain embodimentsare contemplated where the targeting peptide and/or antimicrobialpeptide, and/or STAMP is formulated in combination with one or moresalts. The formulatiosn disclosed herein, however, are not limited tothose containing salt(s). Embodiments, are also contemplated where thetargeting peptide and/or antimicrobial peptide, and/or STAMP isformulated without the presence of a salt.

In certain embodiments, sodium chloride plus a little potassium chlorideresulted in the best activity of the salts tested. However, other salts,e.g., CaCl₂, MgCl₂, MnCl₂ also enhanced activity. Accordingly, incertain embodiments, it is contemplated that the targeting peptide(s),and/or antimicrobial peptide(s), and/or chimeric moieties, and/or STAMPsare formulated with one or more salts.

In certain embodiments suitable salts include any of a number ofpharmaceutically acceptable salts. Representative salts include thehydrobromide, hydrochloride, sulfate, bisulfate, phosphate, nitrate,acetate, valerate, oleate, palmitate, stearate, laurate, benzoate,lactate, phosphate, tosylate, citrate, maleate, fumarate, succinate,tartrate, napthylate, mesylate, besylate, glucoheptonate, lactobionate,and laurylsulphonate salts and the like (see, e.g., Berge et al. (1977)J. Pharm. Sci. 66: 1-19), although it is noted that citrate salts appearto inhibit the activity of certain STAMPs.

In certain embodiments pharmaceutically acceptable salts of the presentinvention include the conventional nontoxic salts or quaternary ammoniumsalts of the compounds, e.g., from non-toxic organic or inorganic acids.For example, such conventional nontoxic salts include those derived frominorganic acids such as hydrochloride, hydrobromic, sulfuric, sulfamic,phosphoric, nitric, and the like; and the salts prepared from organicacids such as acetic, propionic, succinic, glycolic, stearic, lactic,malic, tartaric, citric, ascorbic, palmitic, maleic, hydroxymaleic,phenylacetic, glutamic, benzoic, salicyclic, sulfanilic,2-acetoxybenzoic, fumaric, toluenesulfonic, methanesulfonic,benzenesulfonic, ethane disulfonic, oxalic, isothionic, and the like.

In other cases, the compounds of the present invention may contain oneor more acidic functional groups and, thus, are capable of formingpharmaceutically-acceptable salts with pharmaceutically-acceptablebases. The term “pharmaceutically-acceptable salts” in these instancesrefers to the relatively non-toxic, inorganic and organic base additionsalts of compounds of the present invention. These salts can likewise beprepared in situ in the administration vehicle or the dosage formmanufacturing process, or by separately treating the compound in itsfree acid form with a suitable base, such as the hydroxide, carbonate orbicarbonate of a pharmaceutically-acceptable metal cation, with ammonia,or with a pharmaceutically-acceptable organic primary, secondary ortertiary amine. Representative alkali or alkaline earth salts includethe lithium, sodium, potassium, calcium, magnesium, and aluminum saltsand the like. Representative organic amines useful for the formation ofbase addition salts include ethylamine, diethylamine, ethylenediamine,ethanolamine, diethanolamine, piperazine and the like (see, for example,Berge et al., supra; and Stahl and Wermuth (2002) Handbook ofPharmaceutical Salts: Properties, Selection, and Use, Wiley-VCH, Zurich,Switzerland).

In various embodiments, the salt is simply a sodium chloride and/or apotassium chloride and can readily be prepared, for example, as aphosphate buffered saline (PBS) solution. In certain embodiments, thesalt concentration is comparable to that found in 0.5×PBS to about2.5×PBS, more preferably from about 0.5×PBS to about 1.5×PBS. In certainembodiments optimum activity has been observed in 1×PBS.

In various embodiments, the pH of the formulation ranges from about pH5.0 to about pH 8.5, preferably from about pH 6.0 to about pH 8.0, morepreferably from about pH 7.0 to about pH 8.0. In certain embodiments thepH is about pH 7.4.

While optimum results have been observed for certain STAMPs using a PBSbuffer system, other buffer systems are also acceptable. Such buffersinclude, but are not limited to sulfate buffers, carbonate buffers, Trisbuffers, CHAPS buffers, PIPES buffers, and the like, as long as the saltis included.

In various embodiments, the targeting peptide, and/or antimicrobialpeptide, and/or chimeric moiety, and/or STAMP is present in theformulation at a concentration ranging from about 1 nM, to about 1, 10,or 100 mM, more preferably from about 1 nM, about 10 nM, about 100 nM,about 1 μM, or about 10 μM to about 50 μM, about 100 μM, about 200 μm,about 300 μM, about 400 μM, or about 500 μM, preferably from about 1μL1M, about 10 μM, about 25 μM, or about 50 μM to about 1 mM, about 10mM, about 20 mM, or about 5 mM, most preferably from about 10 μM, about20 μM, or about 50 μM to about 100 μM, about 150 μM, or about 200 μM.

D) Home Health Care/Hygiene Product Formulations.

In certain embodiments, one or more of the targeting peptide(s), and/orantimicrobial peptides (AMPs) and/or chimeric moieties, and/or STAMPSdescribed herein are incorporated into healthcare formulations, e.g.,for home use. Such formulations include, but are not limited totoothpaste, mouthwash, tooth whitening strips or solutions, contact lensstorage, wetting, or cleaning solutions, dental floss, toothpicks,toothbrush bristles, oral sprays, oral lozenges, nasal sprays,aerosolizers for oral and/or nasal application, wound dressings (e.g.,bandages), and the like.

For example, chimeric moieties and/or STAMPs, and/or AMPs directedagainst S. mutans are well suited for inhibiting frequency or severityof dental caries formation, plaque formation, periodontal disease,and/or halitosis.

Chimeric moieties and/or STAMPs, and/or AMPs directed againstCorynebacterium spp, when applied to a skin surface can reduce/eliminateCorynebacterium resulting in a reduction of odors. Such moieties arereadily incorporated in soaps, antibiotics, antiseptics, disinfectants,and the like.

The formulation of such health products is well known to those of skill,and the antimicrobial peptides and/or chimeric constructs are simplyadded to such formulations in an effective dose (e.g., a prophylacticdose to inhibit dental carie formation, etc.).

For example, toothpaste formulations are well known to those of skill inthe art. Typically such formulations are mixtures of abrasives andsurfactants; anticaries agents, such as fluoride; tartar controlingredients, such as tetrasodium pyrophosphate and methyl vinylether/maleic anhydride copolymer; pH buffers; humectants, to preventdry-out and increase the pleasant mouth feel; and binders, to provideconsistency and shape (see, e.g., Table 17). Binders keep the solidphase properly suspended in the liquid phase to prevent separation ofthe liquid phase out of the toothpaste. They also provide body to thedentifrice, especially after extrusion from the tube onto thetoothbrush.

TABLE 17 Typical components of toothpaste. Ingredients Wt % Humectants40-70 Water  0-50 Buffers/salts/tartar 0.5-10  control Organicthickeners 0.4-2   (gums) Inorganic thickeners  0-12 Abrasives 10-50Actives (e.g., triclosan) 0.2-1.5 Surfactants 0.5-2   Flavor andsweetener 0.8-1.5 Fluoride sources provide 1000-15000 ppm fluorine.

Table 18 lists typical ingredients used in formulations; the finalcombination will depend on factors such as ingredient compatibility andcost, local customs, and desired benefits and quality to be delivered inthe product. It will be recognized that one or more antimicrobialpeptides and/or chimeric constructs described herein can simply be addedto such formulations or used in place of one or more of the otheringredients.

TABLE 18 List of typical ingredients. Tartar Inorganic Control GumsThickeners Abrasives Surfactants Humectants Ingredient Sodium SilicaHydrated Sodium Glycerine Tetrasodium carboxymethyl thickeners silicalauryl sulfate pyrophosphate cellulose Cellulose ethers Sodium DicalciumSodium N- Sorbitol Gantrez S-70 aluminum phosphate lauryl silicatesdigydrate sarcosinate Xanthan Gum Clays Calcium Pluronics PropyleneSodium tri- carbonate glycol polyphosphate Carrageenans Sodium Xylitolbicarbonate Sodium alginate Calcium Sodium Polyethylene pyrophosphatelauryl glycol sulfoacetate Carbopols Alumina

One illustrative formulation described in U.S. Pat. No. 6,113,887comprises (1) a water-soluble bactericide selected from the groupconsisting of pyridinium compounds, quaternary ammonium compounds andbiguanide compounds in an amount of 0.001% to 5.0% by weight, based onthe total weight of the composition; (2) a cationically-modifiedhydroxyethylcellulose having an average molecular weight of 1,000,000 orhigher in the hydroxyethylcellulose portion thereof and having acationization degree of 0.05 to 0.5 mol/glucose in an amount of 0.5% to5.0% by weight, based on the total weight of the composition; (3) asurfactant selected from the group consisting of polyoxyethylenepolyoxypropylene block copolymers and alkylolamide compounds in anamount of 0.5% to 13% by weight, based on the total weight of thecomposition; and (4) a polishing agent of the non-silica type in anamount of 5% to 50% by weight, based on the total weight of thecomposition. In certain embodiments, the antimicrobial peptide(s) and/orchimeric construct(s) described herein can be used in place of thebactericide or in combination with the bactericide.

Similarly, mouthwash formulations are also well known to those of skillin the art. Thus, for example, mouthwashes containing sodium fluorideare disclosed in U.S. Pat. Nos. 2,913,373, 3,975,514, and 4,548,809, andin US Patent Publications US 2003/0124068 A1, US 2007/0154410 A1, andthe like. Mouthwashes containing various alkali metal compounds are alsoknown: sodium benzoate (WO 9409752); alkali metal hypohalite (US20020114851A1); chlorine dioxide (CN 1222345); alkali metal phosphate(US 2001/0002252 A1, US 2003/0007937 A1); hydrogen sulfate/carbonate (JP8113519); cetylpyridium chloride (CPC) (see, e.g., U.S. Pat. No.6,117,417, U.S. Pat. No. 5,948,390, and JP 2004051511). Mouthwashescontaining higher alcohol (see, e.g., US 2002/0064505 A1, US2003/0175216 A1); hydrogen peroxide (see, e.g., CN 1385145); CO₂ gasbubbles (see, e.g., JP 1275521 and JP 2157215) are also known. Incertain embodiments, these and other mouthwash formulations can furthercomprise one or more of the AMPs or compound AMPs of this invention.

Contact lens storage, wetting, or cleaning solutions, dental floss,toothpicks, toothbrush bristles, oral sprays, oral lozenges, nasalsprays, and aerosolizers for oral and/or nasal application, and the likeare also well known to those of skill in the art and can readily beadapted to incorporate one or more antimicrobial peptide(s) and/orchimeric construct(s) described herein.

The foregoing pharmaceutical and/or home healthcare formulations and/ordevices are meant to be illustrative and not limiting. Using teachingprovided herein, the antimicrobial peptide(s) and/or chimericconstruct(s) described herein can readily be incorporated into otherproducts.

E) Illustrative Oral Care Formulations.

The targeting peptide(s), and/or antimicrobial peptide(s), and/orchimeric moieties, and/or STAMPs described herein can be used for anumber of applications, e.g., as described above. In certain embodimentsanti-S. mutans STAMPs, AMPs, and/or other chimeric moieties can be usedto reduce the incidence or severity of dental caries, inhibit plaqueformation, reduce halitosis, and the like. Accordingly, in certainembodiments, such moieties are included in devices and formulations fordental applications e.g., tea or other drinks, toothpick coatings,dental floss coatings, toothpaste, gel, mouthwash, varnish, evenprofessional dental products.

In certain embodiments, methods of treating or reducing the incidence,duration, or severity of periodontal disease are provided. The methodscan include applying to the gingival crevice or periodontal pocket acomposition comprising a targeting peptide, and/or antimicrobialpeptide, and/or STAMP, and/or other chimeric moiety as described hereinwith a carrier/stabilizing agent. In the composition applied, thecarrier/stabilizing agent can provide retention, tissue penetration,deposition and sustained release of the active agent (e.g., STAMP) forreducing the population of specific bacterial species within aperiodontal biofilm and associated tissues. In certain embodiments, thecarrier agent provides penetration and retention into the gingivalcrevice or periodontal pocket and associated tissues with sustainedrelease of the active agent to enhance the reduction in population ofselect bacteria within the gingival tissue and dentinal tubule tissue.

In various embodiments, carrier agents can include, but are not limitedto polylactide, polyglycolide, polylactide-co-glycolide,polycaprolactone, cellulosic-based polymers, ethylene glycol polymersand its copolymers, oxyethylene polymers, polyvinyl alcohol, chitosanand hyaluronan and its copolymers. In an aspect, the carrier agentsinclude hydroxyethyl cellulose, hydroxypropyl cellulose,hydroxypropylmethyl cellulose, hydroxymethyl cellulose, polyvinylalcohol, polyethylene glycol, polyethylene oxide, ethyleneoxide-propylene oxide co-polymers, chitosan, hyaluronan and itscopolymers, or combinations thereof. In another aspect, the carrieragents include hyaluronan or hyaluronic acid and copolymers includingsalts of hyaluronic acid, esters of hyaluronic acid, cross-linked gelsof hyaluronic acid, enzymatic derivatives of hyaluronic acid, chemicallymodified derivatives of hyaluronic acid or combinations thereof. As usedherein, hyaluronic acid broadly refers to naturally occurring, microbialand synthetic derivatives of acidic polysaccharides of various molecularweights constituted by residues of D-glucuronic acid polysaccharides andN-acetyl-D-glucosamine.

In certain embodiments, the active agent (e.g., STAMP, AMP, etc.) andthe carrier agent are in the form of an admixture, in the form of acomplex, covalently coupled, or a combination thereof. In certainembodiments, the carrier agent comprises a bioadhesive. Suitablebioadhesive carrier agents include, but are not limited to a cellulosebased polymer and/or a dextrin. Suitable cellulose based polymersinclude, but are not limited to hydroxyethyl cellulose, hydroxypropylcellulose, hydroxymethyl cellulose, or a mixture thereof. In oneillustrative embodiment, the bioadhesive carrier agent includespolylactide, polyglycolide, polylactide-co-glycolide, polyethyleneglycol, hyaluronan, hyaluronic acid, chitosan, or a mixture thereof. Incertain embodiments the bioadhesive carrier agent can include acopolymer comprising polyethylene glycol, hyaluronan, hyaluronic acid,chitosan, or a mixture thereof.

In certain embodiments, the carrier agent penetrates periodontaltissues. Suitable penetrating carrier agents include, but are notlimited to hyaluronic acid, a hyaluronic acid derivative, chitosan, achitosan derivative, or a mixture thereof. In an embodiment, thepenetrating carrier agent includes a salt of hyaluronic acid, an esterof hyaluronic acid, an enzymatic derivative of hyaluronic acid, across-linked gel of hyaluronic acid, a chemically modified derivative ofhyaluronic acid, or a mixture thereof.

V. Microorganism Detection.

As indicated above, the targeting moieties and/or STAMPs are useful indiagnostic compositions and methods to determine the presence or absenceand/or to quantify the amount of one or microorganisms present in theenvironment, in a food stuff, in a biological sample, and the like.

For example, targeting peptide-antimicrobial peptide conjugates (e.g.Specifically targeted antimicrobial peptides (STAMPs)) can be used asdiagnostic reagents. STAMPs (and other targeted antimicrobial constructsdescribed herein) have the ability to specifically bind tomicroorganisms, for example, S. mutans, and permeabilize or disrupttheir membrane such that cell impermeable dyes or other reagent(propidium iodide, etc.) may enter the microorganism or intracellularmolecules or contents (ATP, DNA, Calcium, etc.) of the targetedmicroorganism are caused to be released into the environment foranalysis. In one method a STAMP, for example, C16G2, can permeabilize ordisrupt the membrane of target microorganisms, for example, S. mutans,in a prepared culture or clinical sample by itself, in a biofilm invitro or in vivo. To the sample a cell impermeable dye (e.g. propidiumiodide, etc.) is added to label and allow for detection of thosemicroorganisms targeted by the STAMP. Cell permeable dyes (e.g. SYTO9)can also be added to label and detect the entire population ofmicroorganisms in the sample. Labeled cells can then be quantified byfluorescence microscopy, fluorometry, flow cytometry or other method.

In another example, a STAMP treated sample is mixed with luciferase andluciferin which reacts with the ATP released from the STAMP treatedcells and the resulting luminescence is used to detected and quantifytargeted cells.

VI. Kits.

In another embodiment this invention provides kits for the inhibition ofan infection and/or for the treatment and/or prevention of dental cariesin a mammal. The kits typically comprise a container containing one ormore of the active agents (i.e., the antimicrobial peptide(s) and/orchimeric construct(s)) described herein. In certain embodiments theactive agent(s) can be provided in a unit dosage formulation (e.g.,suppository, tablet, caplet, patch, etc.) and/or may be optionallycombined with one or more pharmaceutically acceptable excipients.

In certain embodiments the kits comprise one or more of the homehealthcare product formulations described herein (e.g., toothpaste,mouthwash, tooth whitening strips or solutions, contact lens storage,wetting, or cleaning solutions, dental floss, toothpicks, toothbrushbristles, oral sprays, oral lozenges, nasal sprays, aerosolizers fororal and/or nasal application, and the like).

In certain embodiments kits are provided for detecting and/or locatingand/or quantifying certain target microorganisms and/or cells or tissuescomprising certain target microorganisms, and/or prosthesis bearingcertain target microorganisms, and/or biofilms comprising certain targetmicroorganisms. In various embodiments these kits typically comprise achimeric moiety comprising a targeting moiety and a detectable label asdescribed herein and/or a targeting moiety attached to an affinity tagfor use in a pretargeting strategy as described herein.

In addition, the kits optionally include labeling and/or instructionalmaterials providing directions (i.e., protocols) for the practice of themethods or use of the “therapeutics” or “prophylactics” or detectionreagents of this invention. Certain instructional materials describe theuse of one or more active agent(s) of this invention to therapeuticallyor prophylactically to inhibit or prevent infection and/or to inhibitthe formation of dental caries. The instructional materials may also,optionally, teach preferred dosages/therapeutic regiment, counterindications and the like.

While the instructional materials typically comprise written or printedmaterials they are not limited to such. Any medium capable of storingsuch instructions and communicating them to an end user is contemplatedby this invention. Such media include, but are not limited to electronicstorage media (e.g., magnetic discs, tapes, cartridges, chips), opticalmedia (e.g., CD ROM), and the like. Such media may include addresses tointernet sites that provide such instructional materials.

EXAMPLES

The following examples are offered to illustrate, but not to limit theclaimed invention.

Example 1 Design and Activity of a “Dual-Targeted” Antimicrobial Peptide

Numerous reports have indicated the important role of human normal florain the prevention of microbial pathogenesis and disease. Evidencesuggests that infections at mucosal surfaces result from the outgrowthof subpopulations or clusters within a microbial community, and are notlinked to one pathogenic organism alone. In order to preserve theprotective normal flora while treating the majority of infectivebacteria in the community, a tunable therapeutic is necessary that candiscriminate between benign bystanders and multiple pathogenicorganisms. Here we describe the proof-of-principle for such amulti-targeted antimicrobial: a multiple-headed specifically-targetedantimicrobial peptide (MH-STAMP). The completed MH-STAMP, M8(KH)-20,displays specific activity against targeted organisms in vitro(Pseudomonas aeruginosa and Streptococcus mutans) and can remove bothspecies from a mixed planktonic culture with little impact againstuntargeted bacteria. These results demonstrate that a functional,dual-targeted molecule can be constructed from wide-spectrumantimicrobial peptide precursor.

Introduction

For nearly 30 years antimicrobial peptides (AMPs) have been rigorouslyinvestigated as alternatives to small molecule antibiotics and potentialsolutions to the growing crisis of antibiotic resistant bacterialinfections (Ganz (2003) Nat Rev Immunol., 3: 710-720; Hancock and Lehrer(1998)., 16: 82-88). Numerous reports have characterized potential AMPsfrom natural sources, and a great body of work has been carried outdesigning “tailor-made” AMPs due to the approachable nature ofsolid-phase peptide synthesis (SPPS) (Genco et al. (2003) Int JAntimicrob Agents, 21: 75-78; He and Eckert (2007) Antimicrob AgentsChemother., 51: 1351-1358). Several examples of the latter have shownremarkable activities in vitro against fungi, Gram-positive andGram-negative bacteria, as well as some enveloped viruses (Brogden(2005) Nat Rev Microbiol. 3: 238-250).

Unlike small molecule antibiotics that may lose activity when theirbasic structures are modified even incrementally, peptides are aconvenient canvas for molecular alteration. AMPs can be optimizedthrough the incorporation of more or less hydrophobic or charged aminoacids, which has been shown to affect selectivity for Gram-positive,Gram-negative or fungal membranes (Muhle and Tam J P (2001)Biochemistry, 40: 5777-5785; Tossi et al. (2000) Biopolymers 55: 4-30).Additionally, lysine residues can be utilized to improve AMP activityper μM. In this approach, multiple AMP chains can be attached to asingle peptide scaffold through branching from lysine epsilon-amines(Tam et al. (2992) Eur. J. Biochem., 269: 923-932; Pini et al. (2005)Antimicrob Agents Chemother., 2005; 49: 2665-2672). AMP activity can bespecifically tuned through the attachment of a targeting peptide region,as described for a novel class of molecules, the specifically-targetedantimicrobial peptides, or STAMPs (Eckert et al. (2006) AntimicrobAgents Chemother., 50: 3651-3657; Eckert et al. (2006) Antimicrob AgentsChemother., 50: 1480-1488). These chimeric molecules can consist offunctionally independent targeting and killing moieties within a linearpeptide sequence. A pathogenic bacterium recognized (i.e. bound) by thetargeting peptide can be eliminated from a multi-species community withlittle impact to bystander normal flora. As an extension of thisconcept, we hypothesized that a STAMP could be constructed with multipletargeting peptide “heads” attached to a single AMP by utilizing acentral lysine residue branch point. Potentially, targeting “heads”could be specific for the same pathogen, or have different bindingprofiles. Utilizing the former approach, microbial resistance evolutionlinked to a targeting peptide could be inhibited or reduced, as nosingle microbial population would have the genetic diversity necessaryto mutate multiple discrete targeting peptide receptors in one cell(Drake et al. (1998) Genetics 148: 1667-1686).

Multi-headed STAMP (MH-STAMP) molecules with differing bacterial targetsmay have appeal in treating poly-microbial infections, or where it maybe advantageous to remove a cluster of biofilm constituents withoututilizing several distinct molecules; for example in the simultaneouslytreatment of dental caries and periodontitis, or in the eradication ofthe Propionibacteria spp. and Staphylococcus spp. involved in acne andskin infections, respectively.

In this example, we present the proof-of-principle design, synthesis andin vitro activity of such a MH-STAMP, M8(KH)-20. Previously, weidentified two functional STAMP targeting domains, one with specificrecognition of the cariogenic pathogen S. mutans (Eckert et al. (2006)Antimicrob Agents Chemother., 50: 3651-3657), and the other withPseudomonas spp.-level selectivity (Eckert et al. (2006) AntimicrobAgents Chemother., 50: 3833-3838). Conjoined to a normally wide-spectrumlinear AMP, we observed antimicrobial effects directed specifically toP. aeruginosa and S. mutans in vitro. Additionally, treatment of mixedbacterial communities with the multi-headed MH-STAMP resulted in thespecific eradication of the target organisms with little impact onbystander population levels.

Materials and Methods

Bacterial Strains and Growth Conditions

P. aeruginosa ATCC15692, Klebsiella pneumoniae KAY 2026 (Sprenger andLengeler (1984) J Bacteriol., 157: 39-45), Escherichia coli DH5a (pFW5,spectinomycin resistance) (Podbielski et al. (1996) Gene, 177: 137-147),Staphylococcus aureus Newmann (Duthie and Lorenz (1952) J GenMicrobiol., 6: 95-107), and Staphylococcus epidermidis ATCC35984 werecultivated under aerobic conditions at 37° C. with vigorous shakingAerobic Gram-negative organisms were grown in Lauri-Bertaini (LB) brothand Gram-positive bacteria in Brain-heart infusion (BHI) broth.Streptococcus mutans JM11 (spectinomycin resistant, UA140 background)was grown in Todd-Hewitt (TH) broth under anaerobic conditions (80% N2,15% CO₂, 5% H2) at 37° C. Merritt et al. (2005) J Microbiol Meth., 61:161-170. All bacteria were grown overnight to an OD600 of 0.8-1.0 priorto appropriate dilution and antimicrobial testing.

Synthesis of Multi-Head STAMP Peptides

Conventional solid-phase peptide synthesis (SPPS) methodologies wereutilized for the construction of all peptides shown in FIG. 15 (SymphonySynthesizer, PTI, Tucson, Ariz.). Chemicals, amino acids, and synthesisresins were purchased from Anaspec (San Jose, Calif.). BD2.20(FIRKFLKKWLL (SEQ ID NO:3226), amidated c-terminus, mw 1491.92), anantimicrobial peptide developed in our laboratory with robustantimicrobial activity against a number of bacterial species (Table 19),served as the root sequence to which differing targeting peptides wereattached: Firstly, BD2.20 was synthesized by SPPS (Rink-Amide-MBHAresin, 0.015 mmol), followed by the stepwise coupling of afunctionalized alkane (NH₂(CH₂)₇COOH), and an Fmoc-protected Lys(side-chain protected with 4-methyltrityl (Mtt)) to the N-terminus.Standard SPPS methods were then employed for the step-wise addition ofthe S. mutans targeting peptide M8 plus a tri-Gly linker region(TFFRFLNR-GGG (SEQ ID NO:3227)) to the N-terminal of the central Lys.After assembly of Fmoc-M8-GGG-K(Mtt)-(CH₂)₇C0-BD2.20 (SEQ ID NO:3228),the Fmoc group was removed with 25% piperidine in DMF and the N-terminalwas re-protected with an acetyl group with Ac₂O/DIEA (1:1, 20 molarexcess) for 2 hours. The Mtt-protected amino group of the central Lyswas then selectively exposed with 2% TFA in DCM (1.5 mL) for 15 minutes(three cycles of 5 min). The resulting product was reloaded into thesynthesizer and the peptide sequence built from the Lys side-chain wascompleted with standard Fmoc SPPS methods. As shown in FIG. 15, thecompleted MH-STAMP M8(KH)-20 contained the side-chain peptide KH(Pseudomonas spp.-targeting, KKHRKHRKHRKH-GGG (SEQ ID NO:3229)), whilein MH-STAMP M8(BL)-20 a peptide with no bacterial binding (data notshown), BL-1 (DAANEA-GGG), was utilized. BL(KH)-20 was constructedidentically to M8(KH)-20, utilizing BL-1 in place of M8 (FIG. 15).

TABLE 19 MICs of MH-STAMPs and component peptides. MIC (μM) P.aeruginosa E. coli K. pneumoniae S. mutans S. epidermidis S. aureusBD2.20 14.4 ± 4.40 5.47 ± 1.41 2.98 ± 0.47 2.86 ± 0.60 5.11 ± 1.58 5.625± 1.29 M8(KH)- 11.95 ± 3.32  2.72 ± 0.59 3.13 6.25 3.13  5.64 ± 1.07 20M8(BL)- 50 5.97 ± 0.94 6.88 ± 1.98 6.25 6.25 18.05 ± 6.58 20 BL(KH)-27.5 ± 7.90 6.25 6.25 6.25 6.25 6.25 20 Average MIC with standarddeviation, n = 10 assays.

Synthesis progression was monitored by the ninhydrin test, and completedpeptides cleaved from the resin with 95% TFA utilizing appropriatescavengers, and precipitated in methyl tert-butyl ether. Purificationand MH-STAMP quality was confirmed by HPLC (Waters, Milford, Mass.)using a linear gradient of increasing mobile phase (acetonitrile 10 to90% in water with 0.1% TFA) and a Waters XBridge BEH 130 C18 column(4.6×100 mm, particle size 5 μm). Absorbance at 215 nm was utilized asthe monitoring wavelength, though 260 and 280 nm were also collected. LCspectra were analyzed with MassLynx Software v.4.1 (Waters).Matrix-assisted laser desorption ionization (MALDI) mass spectroscopywas utilized to confirm correct peptide mass (Voyager System 4291,Applied Biosystems) (Anderson et al. (2008) Biotechnol Lett., 30:813-818).

MIC Assay

Peptides were evaluated for basic antimicrobial activity by brothmicrodilution, as described previously (Eckert et al. (2006) AntimicrobAgents Chemother., 50: 3651-3657; Eckert et al. (2006) Antimicrob AgentsChemother., 50: 1480-1488). Briefly, ˜1×105 cfu/mL bacteria were dilutedin TH (S. mutans), or Mueller-Hinton (MH) broth (all other organisms)and distributed to 96-well plates. Serially-diluted (2-fold) peptideswere then added and the plates incubated at 37° C. for 18-24 h. PeptideMIC was determined as the concentration of peptide that completelyinhibited organism growth when examined by eye (clear well). Allexperiments were conducted 10 times.

Post-Antibiotic Effect Assay

The activity and selectivity of MH-STAMPs after a 10 min incubation wasdetermined by growth retardation experiments against targeted anduntargeted bacteria in monocultures, as described previously (Id.).Cells from overnight cultures were diluted to ˜5×106 cfu/mL in MH (or THwith 1% sucrose for S. mutans), normalized by OD600 0.05-0.1 and seededto 96-well plates. Cultures were then grown under the appropriateconditions for 2 h (3 h for S. mutans) prior to the addition of peptidesfor 10 min. Plates were then centrifuged at 3000×g for 5 min, thesupernatants discarded, fresh medium returned (MH or TH without sucrosefor S. mutans), and incubation resumed. Bacterial growth after treatmentwas then monitored over time by OD600.

Microbial Population Shift Assay

Mixed planktonic populations of P. aeruginosa, E. coli, S. epidermidis,and S. mutans were utilized to examine the potential of MH-STAMPs todirect species composition within a culture after treatment. Sampleswere prepared containing: ˜6×10⁴ cfu/mL S. mutans, ˜2×10⁴ cfu/mL E.coli, ˜2×10⁴ cfu/mL S. epidermidis, and ˜0.5×10⁴ cfu/mL P. aeruginosa inBHI (mixed immediately before peptide addition). Peptide (10 μM) ormock-treatment (1×PBS) was then added and samples were incubated at 37°C. for 24 h under anaerobic conditions (80% N₂, 15% CO₂, 5% H₂). Afterincubation, samples were serially diluted (1:10) in 1×PBS and aliquotsfrom each dilution were then spotted to agar plates selective for eachspecies in the mixture: TH plus 800 μg/mL spectinomycin (S. mutans), LBplus 25 μg/mL ampicillin (P. aeruginosa), LB plus 200 μg/mLspectinomycin (E. coli), and mannitol salt agar (MSA, S. epidermidis) inorder to quantitate survivors from each species. Plates were thenincubated 37° C. under aerobic conditions (TH plates were incubatedanaerobically) and colonies counted after 24 h to determine survivors.Expected colony morphologies were observed for each species when platedon selective media. Gram stains and direct microscopic observation (fromselect isolated colonies) were undertaken to confirm species identity(data not shown). The detection limit of the assay was 200 cfu/mL.

Results

Design and Synthesis of Multi-Headed STAMPs

We constructed a prototype MH-STAMP from the well-established targetingpeptides KH (specific to Pseudomonas spp) and M8 (specific forStreptococcus mutans). The wide-spectrum antimicrobial peptide BD2.20was utilized as the base AMP for all MH171 STAMP construction. BD2.20 isa novel synthetic AMP with a cationic and amphipathic residuearrangement, which has robust MICs against a variety of Gram-negativeand Gram-positive organisms (Table 19). For the synthesis of MH-STMAPM8(KH)-20 (construct presented in FIG. 15), BD2.20 and a Lys(Mtt-protected side-chain) residue were joined via an activated alkanespacer, followed by addition of the M8 targeting peptide to theN-terminus of the product. Selective deprotection of the centralLys(Mtt) side chain was then undertaken and the KH targeting peptideattached. The correct molecular mass (4888.79) and ˜90% purity wasconfirmed by HPLC and MALDI mass spectrometry (FIG. 16).

The non-binding “blank” targeting peptide BL-1 was incorporated into thesynthesis scheme in place of KH or M8 to construct variant MH-STAMPspossessing a single functional targeting head: M8(BL)-20 and BL(KH)-20.The correct MW and acceptable purity were observed for these MH-STAMPs(FIG. 15, data not shown).

General Antimicrobial Activity of Multi-Head Constructs

After synthesis, the completed MH-STAMPs were evaluated for generalantimicrobial activity by MIC against a panel of bacteria. As shown inTable 19, the MH-STAMP constructs M8(KH)-20, BL(KH)-20, and M8(BL)-20were found to have similar activity profiles to that of BD2.20 for theorganisms examined (less than two titration steps in 10-folddifference). Additionally, we observed a difference in generalsusceptibility between P. aeruginosa and the other organisms tested,suggesting this bacterium is more resistant to BD2.20. Overall, thesedata indicate that the addition of the targeting domains to the basesequence was tolerated and did not completely inhibit the activity ofthe antimicrobial peptide.

Peptide selectivity could not be determined utilizing these methods, asSTAMPs and their parent AMP molecules often display similar MICs, buthave radically different antimicrobial kinetics and selectivity due toincreased specific-killing mediated by the targeting regions (Id.).Therefore, we performed different experiments to test for antimicrobialselectivity and functional MH-STAMP construction.

Selectivity and Post-Antibiotic Effect of MH-STAMP Constructs

MH-STAMP antimicrobial kinetics was ascertained utilizing a variation ofthe classical post-antibiotic effect assay, which measures the abilityof an agent to affect an organism's growth after a short exposureperiod. Monocultures of MH-STAMP-targeted and untargeted organisms wereexposed to M8(KH)-20, M8(BL)-20, BL(KH)-20, or unmodified BD2.20, thenallowed to recover. As shown in FIG. 17A, S. mutans growth waseffectively retarded by M8-containing constructs (M8(KH)-20, M8(BL)-20),but was not altered by a MH-STAMP construct lacking this region(BL(KH)-20). Similarly, the growth of the other targeted bacterium, P.aeruginosa, was inhibited in a KH-dependant manner (FIG. 17B). Incomparison, the non-targeted bacteria E. coli, S. aureus, and S.epidermidis were not inhibited by treatment with any MH-STAMP and wereonly inhibited by the base antimicrobial peptide BD2.20, which displayedrobust antimicrobial activity against all examined strains. Theseresults indicate that MH-STAMPs containing KH or M8 targeting domainshave activity against P. aeruginosa or S. mutans, respectively, and notother bacteria. Furthermore, replacement of the targeting region with anon-binding peptide abolishes specific activity.

Ability of MH-STAMPs to Direct a “Population Shift” within a MixedSpecies Population

We hypothesized that potential MH-STAMP dual-functionality could affecta particular set of bacteria within a mixed population, therebypromoting the outgrowth of non-targeted organisms and “shifting” theconstituent makeup. To examine this possibility, defined mixedpopulations of planktonic cells were treated continuously and themake-up of the community examined after 24 h. As shown in FIG. 18,treatment with the wide spectrum AMP BD2.20 resulted in a significantloss of recoverable cfu/mL after 24 h from all species in the mixture.Treatment with M8(KH)-20 was found to alter this pattern; we observed˜1×10⁵ cfu/mL surviving E. coli and S. epidermidis, but did not recoverS. mutans or P. aeruginosa cfu/mL. In BL(KH)-20 treated samples, P.aeruginosa cfu/mL were not observed, though we recovered higher thaninput cfu/mL from S. mutans and unchanged numbers of S. epidermidis andE. coli. In samples exposed to M8(BL)-20, S. mutans recoverable cfu/mLwere greatly reduced compared to input cfu/mL, while other species werenot affected or affected to a lesser extent. Interestingly, theseresults suggest that M8(KH)-20, M8(BL)-20, and BL(KH)-20 retain theirability to affect organisms recognized by the targeting regions present,even within a mixed population of bacteria.

Discussion

Our results indicate that we have successfully constructed a STAMP withdual antimicrobial specificities controlled by the targeting peptidespresent in the molecule; KH for Pseudomonas spp, M8 for S. mutans. In aclosed multi-species system (FIG. 18), the dual specificity of M8(KH)-20was readily discernable: the population of the culture “shifted” awayfrom targeted organisms after MH-STAMP treatment. The targeted bacteriawere eliminated and the population of untargeted organisms increased, tovarying degrees, above-input cfu/mL. Additionally, interruption of KH orM8 in the MH-STAMP construct with the non-binding peptide BL-1 resultedin the expected elimination of only one targeted species. These resultssupport the hypothesis that functional MH-STAMPs could be constructedfrom a wide-spectrum AMP base.

The emergence of metagenomics and the development of more sensitivemolecular diagnostics has driven an increase in the understanding ofhuman-associated microbial ecologies and host-microbe interactions (Aaset al. (2005) J Clin Microbiol., 43: 5721-5732; Boman (2000) ImmunolRev., 173: 5-16; Kreth et al. (2005) J Bacteriol., 187: 7193-7203). Atmucosal surfaces, it has become clear that our bodies harbor anabundance of residential flora which may impact innate and humoralimmunity, nutrient availability, protection against pathogens, and evenhost physiology (Metges (2000) J Nutr., 130: 1857S-64; Sears (2005)Anaerobe, 11: 247-251; Lievin-Le et al. (2006) Clin Microbiol Rev., 19:315-337; DiBaise et al. (2008) Mayo Clinic Proceedings 83: 460-469).Furthermore, findings have indicated that shifts in the diversity ofnormal flora are associated with negative clinical consequences; forexample the overgrowth of S. mutans in the oral cavity duringcariogenesis (linked to the uptake of sucrose) or theantibiotic-assisted colonization of the intestine by Clostridiumdifficle (Loesche (1986) Microbiol Rev., 50: 353-380; Gould and McDonald(2998) Crit. Care 12: 203). Other population shifts may be linked toaxilla odor (Corynebacteria spp) (Leyden et al. (1981) J InvestDermatol., 77: 413-416; Elsner (2006) Curr Probl Dermatol., 33: 35-41),or even host obesity. Given the quantity and diversity of microbespresent, pathogenesis at mucosal surfaces is not likely to be associatedwith the overgrowth of a single strain or species. More often, it is apopulation shift resulting in the predominance of two or more species;for example the persistence of Burkholderia cepacia and P. aeruginosa incystic fibrosis airway or Treponema denticola and Porphymonas gingivalisand other “red cluster” organisms in gingivitis (Govan and Deretic(1996) Microbiol Rev., 60: 539-574; Paster et al. (2001) J Bacteriol.,183: 3770-3783). In many cases (such as the latter) these species mayhave only distant phylogenetic relationships and display differentialsusceptibilities to antibiotic therapies resulting in persistent diseaseprogression despite treatment (Schlessinger (1988) Clin Microbiol Rev.,1: 54-59; Tresse et al. (1997) J Antimicrob Chemother., 40: 419-421).Currently, available treatments for infections of mucosal surfaces arelargely non-specific (traditional small-molecule antibiotics, mechanicalremoval), and thus are not effective in retaining flora or shifting theconstituent balance back to a health-associated composition (Keene andShklair (1974) J Dent Res., 53: 1295). There is a need for a therapeutictreatment that can selectively target multiple pathogens, regardless oftheir phylogenetic relationship, and MH-STAMPs can help achieve thisgoal.

In monoculture experiments (FIG. 17), our results suggest that M8 or KHinclusion in the MH-STAMP drove activity towards S. mutans or P.aeruginosa, but also that the presence of a targeting domain reduced theactivity of the parent AMP BD2.20 against untargeted organisms. Incontrast, the results of our MIC assays (Table 19) indicate littledifference in activity between BD2.20 and any MH-STAMP. Againstuntargeted organisms, the M8 and KH regions are likely to have anegative, but not completely inhibitory, impact on BD2.20 activity.Given the long duration of activity and the lower inoculum size in theMIC assay (compared with experiments in FIG. 17), it is likely that allBD2.20-containing peptides could reach equal levels of growthinhibition, despite large and target-specific differences inantimicrobial speed. This pattern of results was also observed whencomparing MICs of targeted and untargeted organisms utilizing STAMPsagainst S. mutans and Pseudomonas mendocina (Eckert et al. (2006)Antimicrob Agents Chemother., 50: 3651-3657; Eckert et al. (2006)Antimicrob Agents Chemother., 50: 1480-1488).

Although more rigorous studies and a more medically relevant combinationof pathogen targets is desirable, these findings indicate that it ispossible to design an antimicrobial peptide-based therapeutic withmultiple and defined fidelities in vitro. MH-STAMPs may help improvehuman health through the promotion of healthy microbial constituencies.

Example 2 Synthesis of Peptide—Porphyrin Conjugate

The mixture of coupling reagent HATU (5 eq. excess, 10 mg) andpurpurin-18 (MW 564, 5 eq excess, 15 mg) in 600 mL dry dichloromethane(DCM):DMF:dimethylsulphoxide (DMSO) (1:1:1 (v/v)) was added to thepeptide resin (1 molar equivalent, 15 mg) which was swelled by placingin minimal DMF for 30 min prior to reaction. 26 μL (10 molarequivalents) DIPEA was then added to the reaction flask to initiate thereaction. The reaction mixture was protected with argon and stirred atroom temperature for 3 h.

After finishing, the reaction mixture was then passed down a sinteredglass filtered vial and extensively washed with DMF and DCM to removeall waste reagents. The resin was then dried overnight in vacuum, andcleaved with 1 ml of trifluoroacetic acid (TFA)/thioanisole/water/EDT(10/0.5/0.5/025) for 2 hr at room temperature, and the cleavage solutionwas precipitated with 10 mL methyl-tert butyl ether. The precipitate waswashed twice with the same amount of ether.

Example 3 Synthesis of Peptide—CSA Conjugate

To the fully protected peptide (solution of B43-GGG (FIDSFIRSF-GGG,0.025 mmol) and tri-Boc-CSA-15 (0.0125 mol) in 300 μL DMF, DCC (7.7 mg),HOBt (5.1 mg) and 13 μL DIEA were added in iced-bath. After stirred atroom temperature for four days, the reaction mixture was poured into 5ml water and extracted with chloroform (5×3 mL). The CHCl₃ extract wasevaporated under vacuum and dried in a lyophilizer overnight. The driedCHCl₃ extracts was then dissolved in 1 mL DCM followed by added 1 mL ofTFA in iced-bath. The reaction mixture was further stirred at roomtemperature for 2 hours and precipitated with methyl tert-butyl ether(10 mL). The precipitate was further washed once with the same amountether and dried in vacuum.

Example 4

STAMPs Against Corvnebacterium jeikeium and Streptococcus mutans

This example illustrates the development of STAMPs to selectively targetand reduce or eliminate Streptococcus mutans (dental caries) orCorynebacterium jeikeium (body odor, opportunistic infections) frommixed microbial populations.

Axilla odor is caused by overgrowth of, and metabolite production from,Corynebacterium spp, which replaces Staphylococcus and Micrococcus sppassociated with less odor. Current hygiene (soaps, antibiotics,antiseptics, disinfectants) practices remove all bacteria, allowing theratio of Corynebacteria to normal flora to remain high during regrowth.Deodorants and anti-perspirants are temporary solutions that hide oreven exacerbate the problem.

S. mutans is the major etiological agent of dental caries. Currentmethods (tooth brushing, antiseptic mouthrinses) to treat cariogenesishave focused on complete bacterial removal, i.e., elimination of S.mutans and other harmless oral bacteria. Caries have persisted despitethese methods, and in many cases, S. mutans can become the dominantorganism in the mouth. Several S. mutans and acid-targeted approaches(probiotic replacement, saliva pH adjustment) are under development, butnone have shown clinical efficacy.

This example describes a number of STAMPs that preferentially orselectively reduce or eliminate S mutans and/or Corynebacterium spp frommixed populations.

Several lead STAMPs with specific activity against Corynebacteriumjeikeium are also disclosed herein.

The STAMPs described herein comprise functional regions within a peptidemolecule or a chemical conjugate. These regions include a targetingregion comprising one or more targeting moieties (e.g., targetingpeptides), a linker, and one or more killing moieties (e.g.,antimicrobial peptides (AMPs), porphyrins, etc.).

The STAMPs function through the targeting region, which selectivelyaccumulates STAMPs, and therefore killing regions, on or in proximity tothe microorganism of interest. Other flora are not recognized by thetargeting region, and therefore avoid or have reduced STAMP accumulationand cellular damage.

In certain embodiments, STAMPs against oral S. mutans are best appliedformulated in a mouthrinse, toothpaste, cream, gel, or adhesive strip,and in certain preferably embodiments, are provided in a formulationthat comprises 0.5 to 2.5×PBS (or other salt) and other ingredientscommonly found in oral healthcare formulations (e.g., mouthrinseformulations). Certain illustrative formulations are shown in Table 20.

During the course of evaluating STAMPs, antimicrobial peptides (AMPs),and binding peptides for desired activity, it was discovered thatcertain formulations can attenuate or promote peptide activity, ascompared to activity levels in a default buffer system (1×PBS). In somecases, 1×PBS may provide the best level of activity. Below are a numberof formulations that alter, or may alter, peptide or STAMP activity. Forcomplex buffer systems, assume the base solvent is water unlessotherwise stated.

Formulation 1 (1×PBS, pH 7.4): 136.8 mM NaCl, 2.68 mM KCl, 1.01 mMNa₂HPO₄, and 1.37 mM KH₂PO₄.

Formulation 2 (HEPES/CTAB): 20 mM HEPES(4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), 150 mM NaCl, 1 mMMgCl₂, and 0.1% CTAB (Cetyl trimethylammonium bromide).

Formulation 3 (TRIS/CTAB): 20 mM Tris (tris(hydroxymethyl)aminomethane),pH 7.5, 150 mM NaCl, 1 mM MgCl₂, and 0.1% CTAB.

Formulation 4: 20 mM HEPES.

Formulation 5: 20 mM Tris, pH 7.5.

Formulation 6: 0.2% CTAB.

Formulation 7: 1% Glycerol.

Formulation 8: 1% Pluronic F108 (nonionic surfactant:α-Hydro-.omega.-hydroxypoly(oxyethylene)poly(oxypropylene)poly(oxyethylene)block copolymer).

Formulation 9: 1% Pluronic F123 (Poly(ethyleneglycol)-block-poly(propylene glycol)-block-poly(ethylene glycol),average M_(a)˜5,800).

Formulation 10:1% Pluronic F17R4 (Poly(propyleneglycol)-block-poly(ethylene glycol)-block-polypropylene glycol), averageM_(a)˜2,700).

Formulation 11: 1% to 7% PEG400.

Formulation 12: 50 mM Urea.

Formulation 13: 10 mM AOT (Sodium bis(2-ethylhexyl) sulfosuccinate).

Formulation 14: 0.5-0.1% Tween 20 (nonionic detergent, also known aspolysorbate 20 or PEG(20) sorbitan monolauratesorbitan monolaurate).

Formulation 15: 0.5-0.1% Tween 80 (nonionic surfactant, C₆₄H₁₂₄O₂₆, alsoknown as polyoxyethylene (20) sorbitan monooleate, (x)-sorbitanmono-9-octadecenoate poly(oxy-1,2-ethanediyl), or POE (20) sorbitanmonooleate).

Formulation 16: 5-10% Ethanol.

Formulation 17: 20% Glycerin.

Formulation 18: 20% Sorbitol.

Formulation 19: 10% Glycerin/10% Sorbitol.

Formulation 20: 0.1% SLS (Sodium lauryl sulfate).

Formulation 21: 1% Pluronic F127 (nonionic suffactant:α-Hydro-.omega.-hydroxypoly(oxyethylene)poly(oxypropylene)poly(oxyethylene)block copolymer).

Formulation 21: 0.1% Tween 20 (nonionic detergent, also known asPolysorbate 20, or PEG(20)sorbitan monolaurate).

Formulation 21: 10% PG (phospholipid gel).

Mouthrinse neat solution #1 (made in 1×PBS): 7% ETOH, 20% Glycerin, 7%PEG 400, and 1% PLURONIC® F127.

Mouthrinse neat solution #2 (made in 1×PBS): 7% ETOH, 20% Sorbitol, 7%PEG 400, and 1% PLURONIC® F127.

Mouthrinse neat solution #3 (made in 1×PBS): 7% ETOH, 20% Glycerin and7% PEG 400.

Mouthrinse neat solution #4 (made in 1×PBS): 7% ETOH, 20% Sorbitol and7% PEG 400.

Other illustrative, but not limiting, mouthrinse formulations are shownin Table 20.

TABLE 20 Illustrative mouthrinse formulations. Rinse# ETOH GlycerinPEG400 F127 Water¹ Fluoride  1 5 22.5 7 1 64.5 187.5  2 6 25 1 0 68 0  36 20 7 0 67 0  4 6 20 1 1 72 0  5 7 25 7 0 61 0  6 7 20 1 0 72 0  7 7 207 0 66 250  8 5 20 7 1 67 0  9 6.472 21.139 5.361 0.722 66.306 250 10 722.5 1 0 69.5 250 11 5 25 1 0 69 250 12 7 20 7 0 66 250 13 5 20 1 1 73250 14 5 25 7 0.5 62.5 250 15 7 25 1 0.5 66.5 250 16 7 25 7 1 60 250 175 25 7 0.5 62.5 0 18 7 20 1 1 71 250 19 6 25 1 1 67 250 20 7 25 7 1 60125 21 5 25 1 0 69 250 22 5 20 1.5 0.5 73 0 23 7 20 1 1 71 250 24 6 20 10 73 250 25 5 22.333 3.778 0.444 68.444 125 26 7 25 1 1 66 0 27 6 25 7 062 250 28 7 20 7 1 65 0 29 7 25 4 1 63 62.5 30 5 25 4 0 66 0 31 5 25 1 168 0 32 7 25 7 1 60 0 33 7 22.5 4 0.5 66 0 34 5 20 4.5 0 70.5 250 35 523 1 0 71 62.5 36 6 20 1 1 72 0 37 5 20 7 1 67 250 38 7 20 1 0 72 0 39 525 4 1 65 250 40 5 22.5 7 0 65.5 0 n1 7 20 7 1 65 0 n2 7 20% 7 1 65 0Sorbitol n3 7 20 7 0 66 0 n4 7 20% 7 0 66 0 Sorbitol ¹1xPBS can besubstituted for water

In certain embodiments, Corynebacterium-specific STAMPs are formulatedin any number of creams, nanoemulsions, lipid micelles, aqueous orno-aqueous gels, sprays, soaps or roll-on bars, or other products usedfor axilla or other hygiene.

STAMP-mediated selective antimicrobial activity can result inpreservation of the normal flora at the oral or axilla mucosal surface,resulting in protective colonization and the conversion of a harmfulflora to a beneficial one. Recurrence of pathogen overgrowth would bereduced, which also limits the amount and frequency (and therefore cost)of STAMP delivery. STAMPs allow for “surgical” antimicrobial precision,which limits antimicrobial resistance evolution as well due to thegeneral mechanism of cell membrane damage mediated by the killingregion.

A number of anti-S. mutans STAMPs (see Table 21) and anti-C. jeikeiumSTAMPs have been designed and tested, some in formulations. All showpotent selective activity against their bacterial targets in vitro,including against biofilm forms. When tested, STAMPs have littlecytotoxicity against cell lines in vitro.

TABLE 21 Illustrative anti-S. mutans STAMPs. SEQ ID STAMP Amino AcidSequence NO 2_1G2 FIKHFIHRFGGGKNLRIIRKGIHIIKKY* 3230 C16AF5TFFRLFNRSFTQALGKGGGFLKFLKKFFKKLKY* 3231 1845L621KFINGVLSQFVLERKPYPKLFKFLRKHLL* 3232 1903-21 NIFEYFLEGGGKLFKFLRKHLL* 3233Single underline is binding peptide. Double underline is antimicrobialpeptide (AMP). No underline is linker. *indicates optionally protected(e.g., amidated) C terminal.

TABLE 22 Illustrative anti-C. jeikeium STAMPs. STAMP Amino Acid SequenceSEQ ID NO 2038L6CAM135 GKAKPYQVRQVLRAVDKLETRRKKGGR 3234PYPGWRLIKKILRVFKGL* 1619- SKRGRKRKDRRKKKANHGKRPNSGGGG 3235 CAM135WRLIKKILRVFKGL* 1599-BD2.16 YSKTLHFADGGGKILKFLFKKVF* 3236 1619-BD2.16SKRGRKRKDRRKKKANHGKRPNSGGG 3237 KILKFLFKKVF* 1904-BD2.16GSVIKKRRKRMSKKKHRKMLRRTRVQR 3238 RKLGKGGGKILKFLFKKVF* Single underlineis binding peptide. Double underline is antimicrobial peptide (AMP). Nounderline is linker. *indicates optionally protected (e.g., amidated) Cterminal.

It was a surprising discovery that certain anti-S. mutans STAMPsrequired a salt in the formulation (e.g., PBS) for optimum activity.Thus, for example, the anti-S. mutans STAMP C16G2(TFFRLFNRSFTQALGKGGGKNLRIIRKGIHIIKKY*, SEQ ID NO:2) comprising theTFFRLFNRSFTQALGK (SEQ ID NO:1) attached to the antimicrobial peptide(AMP) KNLRIIRKGIHIIKKY (SEQ ID NO: 3080) by a peptide linker (GGG) wassubstantially inactive in water-based salt-free buffers andnanoemulsions, but was active in a phosphate buffered saline (PBS)formulation. Suitable PBS formulations ranged from 0.5×PBS to about2.5×PBS with an activity optimum at about 1×PBS. Similar results arebelieved to obtain for other anti-S. mutans STAMPS as well as a numberof other STAMPs. In certain embodiments STAMP stability in solution wasimproved by inclusion of fluoride in mouthrinse.

Example 5 Photodynamic Therapy Targeted Against Streptococcus mutans

Dental caries (tooth decay) is one of the most prevalent and costlyinfectious diseases in the United States. Currently, the annualexpenditures on dental services exceed $85 billion, with the majority ofthese costs attributable to dental caries and its sequelae(www.ada.org/). The oral cavity harbors a complex microbial communityconsisting of over 600 different non-harmful/commensal microbial speciestogether with a limited number of pathogenic bacteria, including themajor etiological agent of dental caries, Streptococcus mutans. Onceestablished, S. mutans generates acid during the fermentation of dietarysugars, which causes the demineralization of tooth structure andinhibits the growth of non-pathogenic commensal bacteria within the samemicrobial niche. Despite diligent use of broad-spectrum antimicrobialcompounds and tooth brushing, S. mutans persists within the oral cavityand causes repeated cycles of cariogenesis. Current “remove all,kill-all” approaches have shown limited efficacy, since a “cleaned”tooth surface provides an equal opportunity for commensal as well aspathogenic bacteria to re-colonize in the non-sterile environment of theoral cavity. To address this shortcoming, we have constructed andevaluated a light-activated S. mutans-selective antimicrobial agent.C16-RB, constructed via conjugation of the S. mutanscompetence-stimulating peptide to the photodynamic dye rose bengal,displays robust anti-S. mutans activity in vitro under blue exposurefrom a handheld dental curing light. C16-RB has reduced activity againstother oral streptococci under mixed biofilm conditions and has limitedcytotoxicity in vitro.

To develop a method of selectively eliminating S. mutans from a dentalbiofilm so that beneficial species exert a protective colonizationeffect and long-term protection from S. mutans re-colonization can beattained we created a novel class of targeted antimicrobials, known asspecifically-targeted antimicrobial peptides, or STAMPs. STAMPs consistof functionally independent, yet conjoined, domains within a linearpeptide sequence; a targeting region and an antimicrobial region. Thetargeting region, which binds specifically to a bacterial species ofinterest, delivers the killing portion of the molecule that consists ofa normally wide-spectrum antimicrobial peptide. Previously, wesuccessfully designed STAMPs against S. mutans by taking advantage ofthe competence stimulating pheromone (CSP) peptide produced by thisorganism that has demonstrated S. mutans-specific recognition. STAMPssynthesized with portions of CSP as targeting domains were capable ofspecific antimicrobial activity against S. mutans, and not other oralstreptococci or non-cariogenic organisms in biofilms.

We hypothesized that targeted killing might be achieved through the useof non-peptide antimicrobial molecules, such as porphyrins or dyesutilized in PDT. Here we present the proof-of-principle construction andin vitro efficacy of the targeted, peptide-guided, photodynamic moleculeC16-RB. C16-RB displays S. mutans selective antimicrobial activity uponblue light activation with limited activity against non-cariogenic oralstreptococci and epithelial cells.

Materials and Methods Synthesis of C16-RB

All amino acids, synthesis resins and reagents were peptide synthesisgrade

(Anaspec, San Jose, Calif.; Fisher Scientific). To construct our C16-RBconjugate, conventional 9-fluorenylmethoxy carbonyl (Fmoc) solid-phasemethodology was employed to synthesize the CSP_(c16) peptide and attachthe succinate and PEG linkers, utilizing double coupling cycles inN-hdroxybenzotrazole, HBTU (O-benzotriazole-N,N, N,N-tetramethyl-uroniumhexafluoro-phosphate) and diisopropyl ethylamine (DIEA), withdimethylformamide (DMF) and N-methylpyrrolidone (NMP) as solvents, asdescribed previously. The peptide resin (1 molar equivalent, 15 mg) wasthen swollen in DMF for 30 min prior to attachment of the PEG terminalamide group to the carboxyl lactone in RB (FIG. 19B). This reaction wascarried out in a mixture of2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate (HATU, 5-molar excess) in dichloromethane(DCM):DMF:dimethylsulphoxide (DMSO) (1:1:1 (v/v)). Ten molar equivalentsof DIEA were added to the reaction flask to initiate the reaction, whichwas protected with argon and stirred at room temperature for 5 h. Aftercompletion, the reaction mixture was passed down sintered glass filteredvial and extensively washed with DMF and DCM to remove all wastereagents. The resin was then dried overnight in vacuum, and cleaved with1 mL of trifluoroacetic acid (TFA)/thioanisole/water/EDT(10/0.5/0.5/025) for 2 hr at room temperature. The cleavage solution wasprecipitated with 10 mL methyl-tert butyl ether, and the precipitate waswashed twice with the same amount of ether. The crude product waspurified via preparative-level HPLC (Source 15RPC column, ACTA purifier,Amersham) and eluted with gradient acetonitrile/water from 10 to 35% in10 min, which was increased to 90% over 8 min before finally beingwashed 15 min with 95% acetonitrile.

C16-RB was purified further to >90% and the molecular mass confirmed viaLC/MS, utilizing increasing hydrophobicity gradient of acetonitrile inwater with 0.01% TFA as described above (Waters X-bridge BEH 130 C18column, 4.6×100 mm, particle size 5 μm, Waters 3100 system). LC spectrawere analyzed with MassLynx Softward v. 4.1 (Waters). C16-RB mass(3118.0) was confirmed by electrospray ionization (ESI) massspectroscopy in linear, positive ion mode. The final product waslyophilized and protected from light at all times. C16-RB was soluble in50% methanol.

Bacterial and Cellular Growth

Streptococcus oralis ATCC10557, Streptococcus gordonii (Challis),Streptococcus sanguinis (NY101), Streptococcus mitis ATCC903,Streptococcus salivarius ATCC13419 and S. mutans wild-type UA140 andJM11 (spectinomycin-resistant) strains were grown in Todd-Hewitt (TH)broth 37° C. in an anaerobic atmosphere of 80% N₂, 10% CO₂, and 10% H₂.BHK-21 (ATCC CRL-10) fibroblasts were propagated in DMEM with 10% FBS, 1mM sodium pyruvate, 100 units/mL penicillin G, and 100 μg/mLstreptomycin at 37° C. with 5% CO₂. Cells were detached with 0.25%trypsin and subcultured as recommended by the supplier.

Photodynamic Antimicrobial Assays Against Biofilms

To evaluate C16-RB against monoculture biofilms, S. mutans UA140 wasgrown overnight in TH prior to inoculation for biofilm formation. Forbiofilms, 1:5000 dilution of overnight culture was made into TH with 1%sucrose in 2 mL centrifuge tubes (200 μL volume) and grown 24 h underanaerobic conditions. After incubation, biofilms were treated for 5 minwith 5 or 25 μM C16-RB or 5 μM RB in 1×PBS, or PBS alone, followed byremoval of supernatant and exposure to 5 min blue light (emission400-550 nm, power 400 mW/cm²) from an Astralis 7 (Ivoclar Vivodent,Austria) handheld LED commonly used as a dental curing light. The lightsource was suspended 4 cm from the tube bottom (even with the mouth ofthe tube). A duplicate set of samples were left covered to serve as darkcontrols. After treatment, biofilms were mechanically disrupted andplated to determine cfu/mL.

To gauge C16-RB selectivity for S. mutans, similar assays were conductedagainst multispecies biofilms. Mixed biofilms were seeded by diluting(1:5000) a mixture of equal parts S. oralis, S. gordonii, S. mitis, S.sanguinis, S. salivarius, and S. mutans JM11 (made from overnightcultures) into TH with 1% sucrose, 1% glucose, and 1% mannose. Biofilmswere incubated and treated as described above with the addition ofvitamin C or potassium gluconate. After the addition of agent and 5 minincubation, biofilms were washed 1× with 1×PBS prior to light exposure.After PDT and biofilm disruption, survivors were plated on TH, and THsupplemented with 800 μg/mL spectinomycin, which allowed forquantitation of surviving total oral streptococci and surviving S.mutans, respectively.

Evaluation of C16-RB Cytotoxicity

The effect of RB and C16-RB on human fibroblasts was ascertained byutilizing the Promega CellTiterGlo assay, as described by themanufacturer. Briefly, fibroblasts were grown to confluence, detached,and seeded to 5,000 cells per well in a 96-well opaque walled, clearbottom 96-well plate (Nunc International). For long-term dark toxicity,cells were allowed to attach to for 18 h before the culture medium wasreplaced with medium plus serially-diluted RB or C16-RB (200 μM to 390nM) or medium alone. After 18-24 h, equal volume Cell Titer Glo reagentwas added to each well and mixed. Luciferace activity was thenquantified to measure cell viability (Varian Fluorometer inBiolumenescence mode). To measure cytotoxicity after RB or C16-RB lightexposure, cells were seeded at ˜10,000 cells per well and allowed toattach for 4 h. Cell growth medium was then replaced with RB or C16-RBcontaining medium, prior to exposure (a single well at a time) with bluelight (400 mW/cm²) suspended ˜3 cm from the well bottom. After exposure,cultures were disrupted with Cell Titer Glo and luciferase activityquantitated as above.

Results

Design of Photodynamic Peptide-Dye Conjugate

For the targeting peptide component of the chimeric molecule, weselected a shortened derivative of S. mutans CSP, CSP_(c16) (sequence:TFFRLFNRSFTQALGK). CSP_(C16) has been utilized successfully as a STAMPtargeting peptide in several constructs, and demonstrates selectivebinding to S. mutans and not other non-cariogenic bacteria. For thephotodynamic dye, we selected rose bengal (RB, FIG. 19A), a xanthene dyewith a demonstrated record of safety as a diagnostic tool in optometry.Unlike TBO or methylene blue, RB is not recognized by efflux pumps, andhas shown robust activity against a variety of bacteria in vitro in thepresence of green or blue light (max absorption ˜549 nm), and can beactivated by a handheld dental curing LED.

C16-RB Synthesis

As shown in FIG. 19B, RB was attached to the N-terminus of CSP_(c16)through a succinate/PEG linker to construct the C16-RB molecule.Conventional solid-phase peptide methods were utilized to synthesizeCSPC₁₆, followed by linker and RB coupling prior to cleavage from theresin. After cleavage, C16-RB was repeatedly purified by LC/MS prior toevaluation. As shown in FIG. 20, over 95% purity was achieved with theexpected mass species observed. The lactone ring in RB was opened as aresult of CSP_(C16) attachment. However, we hypothesized that theconjugate would retain enough singlet-oxygen generating activity for aproof-of-principle demonstration, as other xanthene dyes with activitylack this ring.

C16-RB Efficacy Against Single-Species S. mutans Biofilms

After synthesis, the basic photosensitization potential of C16-RB wasassessed by challenging mature single-species S. mutans biofilms (grown24 h) with C16-RB or unmodified RB, followed by blue emission from adental curing light. As shown in FIG. 21, potent antimicrobial activitywas observed in cultures exposed to C16-RB or RB and blue light: areduction in over 3 log₁₀ from input cfu/mL at 5 or 25 μM. In contrast,appreciable decreases in cfu/mL were not observed in S. mutans treatedwith blue light alone, or 5 μM RB or C16-RB dark controls. Modest darktoxicity was observed in samples treated with 25 μM C16—RB. Overall,these results indicate that the peptide-dye conjugate is active againstS. mutans and at roughly similar levels to the parental RB molecule.

Selective PDT Against Multi-Species Biofilms

C16-RB was next evaluated for selectivity in mixed cultures containingS. mutans and non-cariogenic oral streptococci that compete for the sameniche on the tooth surface. We utilized mixed biofilms of S. mutanstransformed with spectinomycin resistance (strain JM11, Merritt, et al.,2005), plus S. oralis, S. gordonii, S. mitis, S. sanguinis, and S.salivarius. The mixed cultures were grown 24 and then treated with RB orC16-RB as indicated, plus potassium gluconate to minimize killing ofuntargeted bacteria by reducing the superoxide-producing activity of thefree C16-RB not bound to S. mutans. Ethanol treatment served as anindiscriminant killing control. As shown in FIG. 21, RB alone exhibitedstrong indiscriminant photodynamic antimicrobial effects against S.mutans and non-S. mutans in the mixed biofilm system (ratio of survivingS. mutans:non-cariogenic streptococci cfu ˜1). In contrast, C16-RBdisplayed specific photodynamic activity towards S. mutans, and not theother oral streptococci examined, as reflected in the low ratio ofrecovered S. mutans to other streptococci. These results suggest C16-RBhas antimicrobial activity in the presence of blue light that isspecific for S. mutans and dependent on the CSP_(c16) targeting peptide.

Cytotoxicity Against Eukaryotic Cells

Given the demonstrated PDT potential of RB-C16, experiments wereconducted to examine the cytotoxicity for this conjugate and RB alone.IC₅₀s were obtained for BHK cells exposed C16—RB, RB, or Melittin B(positive control for cytotoxicity), with and without blue lightexposure. As shown in Table 23, cytotoxicity was noted for cells exposedto Melittin B at the lowest peptide dilution tested at either 5 min or24 h, with or without light (IC₅₀<1.56 μM), while light-dependenttoxicity was observed only for RB-treated samples. No photo-associatedtoxicity was noted in BHK cells treated with C16-RB, though modestlight-independent cytotoxicity (IC₅₀=90 μM) was detected after 24 h ofexposure. These results suggest that C16-RB is not toxic to BHK cellsafter illumination, and displays mild toxic effects (when compared toMelittin B) after 24 h exposure.

TABLE 23 Cytotoxicity of RB and C16-RB compounds. IC₅₀ (μM) BHK 5 mindark: RB-C16 >100 RB >100 Melittin B <1.56 5 min w/blue light:RB-C16 >100 RB 40 Melittin B <1.56 24 h dark RB-C16 55 RB 90 Melittin B<1.56

It is understood that the examples and embodiments described herein arefor illustrative purposes only and that various modifications or changesin light thereof will be suggested to persons skilled in the art and areto be included within the spirit and purview of this application andscope of the appended claims. All publications, patents, and patentapplications cited herein are hereby incorporated by reference in theirentirety for all purposes.

1. A chimeric construct, said construct selected from the groupcomprising: an effector attached to a peptide targeting moietycomprising an amino acid sequence found in Table 3 and/or Table 12; andan antimicrobial peptide comprising an amino acid sequence found inTable 4 and/or Table 5 attached to a targeting moiety.
 2. The chimericconstruct of claim 1, wherein said targeting moiety is a peptidecomprising an amino acid sequence of a peptide found in Table 3 and/orTable
 12. 3-5. (canceled)
 6. The chimeric construct of claim 1, whereinsaid effector comprises a moiety selected from the group consisting ofan antimicrobial peptide, an antibiotic, a ligand, a lipid or liposome,a agent that physically disrupts the extracellular matrix within acommunity of microorganisms, and a polymeric particle.
 7. The chimericconstruct of claim 1, wherein said effector comprises an antimicrobialpeptide comprising an amino acid sequence found in Table 4, and/or Table5, and/or Table 14, and/or Table
 15. 8. (canceled)
 9. The chimericconstruct of claim 1, wherein said effector comprises an antimicrobialpeptide comprising an amino acid sequence characterized by a motifselected from the group consisting of KIF, FIK, KIH, HIK, and KIV. 10.The chimeric construct of claim 1, comprising a targeting peptidecomprising an amino acid sequence found in Table 3 attached to anantimicrobial peptide comprising an amino acid sequence found in Table 4and/or Table
 5. 11. The chimeric construct of claim 1, comprising anantimicrobial peptide comprising an amino acid sequence found in Table 4attached to a targeting moiety comprising an amino acid sequence foundin Table 3 and/or Table 10, and/or Table
 12. 12. The chimeric constructof claim 1, comprising a targeting peptide comprising an amino acidsequence found in Table 3 attached to an antimicrobial peptidecomprising an amino acid sequence found in Table
 4. 13. The chimericconstruct of claim 1, wherein said targeting moiety is chemicallyconjugated to said effector.
 14. The chimeric construct of claim 13,wherein said targeting moiety is chemically conjugated to said effectorvia a linker.
 15. The chimeric construct of claim 13, wherein saidtargeting moiety is chemically conjugated to said effector via a linkercomprising a polyethylene glycol (PEG).
 16. The chimeric construct ofclaim 13, wherein said targeting moiety is chemically conjugated to saideffector via a non-peptide linker found in Table
 16. 17. The chimericconstruct of claim 1, wherein said targeting moiety is linked directlyto said effector.
 18. The chimeric construct of claim 1, wherein saidtargeting moiety is linked to said effector via a peptide linkage. 19.The chimeric construct of claim 18, wherein said effector comprises anantimicrobial peptide and said construct is a fusion protein.
 20. Thechimeric construct of claim 18, wherein said targeting moiety isattached to said effector by a peptide linker comprising or consistingof an amino acid sequence found in Table
 16. 21. The chimeric constructof claim 1, wherein said construct bears one or more protecting groups.22-24. (canceled)
 25. The chimeric construct of claim 1, wherein saidconstruct is functionalized with a polymer to increase serum halflife.26. (canceled)
 27. A pharmaceutical composition comprising a chimericconstruct of claim 1 in a pharmaceutically acceptable carrier. 28.(canceled)
 29. The composition of claim 27, wherein said composition isformulated for administration by a modality selected from the groupconsisting of intraperitoneal administration, topical administration,oral administration, inhalation administration, transdermaladministration, subdermal depot administration, and rectaladministration.
 30. An antimicrobial composition effective to kill or toinhibit the growth and/or of a microorganism and/or the formation and/ormaintenance of a biofilm, said composition comprising one or moreisolated antimicrobial peptides, the amino acid sequences of saidpeptides comprising one or more sequences selected from the amino acidsequences listed in Table 4 and/or Table
 5. 31. The compositionaccording to claim 30, wherein said composition is effective to kill orinhibit the growth and/or proliferation of a yeast or fungus, and saidcomposition comprises one or more peptides, the amino acid sequences ofsaid peptides comprising one or more sequences selected from the groupof amino acid sequences listed in Table 4 and/or Table 5 identified aseffective to effective to kill or inhibit the growth and/orproliferation of a yeast or fungus.
 32. The composition according toclaim 31, wherein said composition is effective to kill or inhibit thegrowth and/or proliferation of Aspergillus niger and said compositioncomprises one or more peptides, the amino acid sequences of saidpeptides comprising one or more sequences selected from the group ofamino acid sequences listed in Table 4 and/or Table 5 identified aseffective to effective to kill or inhibit the growth and/orproliferation of Aspergillus niger.
 33. The composition according toclaim 31, wherein said composition is effective to kill or inhibit thegrowth and/or proliferation of C. albicans and said compositioncomprises one or more peptides, the amino acid sequences of saidpeptides comprising one or more sequences selected from the group ofamino acid sequences listed in Table 4 and/or Table 5 identified aseffective to effective to kill or inhibit the growth and/orproliferation of C. albicans.
 34. The composition according to claim 31,wherein said composition is effective to kill or inhibit the growthand/or proliferation of T. rubrum and said composition comprises one ormore peptides, the amino acid sequences of said peptides comprising oneor more sequences selected from the group of amino acid sequences listedin Table 4 and/or Table 5 identified as effective to effective to killor inhibit the growth and/or proliferation of T. rubrum.
 35. Thecomposition according to claim 30, wherein said composition is effectiveto kill or inhibit the growth and/or proliferation of a bacterium, andsaid composition comprises one or more peptides, the amino acidsequences of said peptides comprising one or more sequences selectedfrom the group of amino acid sequences listed in Table 4 and/or Table 5identified as effective to effective to kill or inhibit the growthand/or proliferation of a bacterium. 36-55. (canceled)
 56. Thecomposition of claim 30, wherein said peptides comprise all “L” aminoacids.
 57. The composition of claim 30, wherein said peptides compriseall “D” amino acids.
 58. The composition of claim 30, wherein saidpeptides comprise a mixture of “L” and “D” amino acids.
 59. Thecomposition of claim 30, wherein said peptides are β peptides.
 60. Thecomposition of claim 30, wherein said peptides comprise one or moreprotecting groups. 61-65. (canceled)
 66. A method of killing and/orinhibiting the growth and/or proliferation of a microorganism, saidmethod comprising contacting said microorganism with a chimericconstruct of claim 1, or a composition of claim
 30. 67. The method ofclaim 66, wherein said microorganism is a yeast or fungus and saidchimeric construct or composition is a chimeric construct of claim 1comprising an effector identified as killing a yeast or fungus, or abinding moiety identified as binding a yeast or fungus. 68-80.(canceled)
 81. A method of detecting a bacterium and/or a bacterialfilm, said method comprising: contacting said bacterium or bacterialfilm with a composition comprising a detectable label attached to atargeting peptide comprising one or more amino acid sequences foundTable 3 and/or Table 12; and detecting said detectable label wherein thequantity and/or location of said detectable label is an indicator of thepresence of said bacterium and/or bacterial film.
 82. The method ofclaim 81, wherein said targeting peptide comprises or consists of anamino acid sequence of a peptide found in Table
 3. 83. The method ofclaim 81, wherein said detectable label is a label selected from thegroup consisting of a radioactive label, a radio-opaque label, afluorescent dye, a fluorescent protein, an enzymatic label, acolorimetric label, and a quantum dot.
 84. A composition comprising aphotosensitizing agent attached to a targeting peptide comprising anamino acid sequence of a peptide found in Table 3 and/or Table
 12. 85.The composition of claim 84, wherein said targeting peptide comprises orconsists of an amino acid sequence of a peptide found in Table
 3. 86.The composition of claim 84, wherein said photosensitizing agent is anagent selected from the group consisting of a porphyrinic macrocycle, aporphyrin, a chlorine, a crown ether, an acridine, an azine, aphthalocyanine, a cyanine, a cucumin, a psoralen, and aperylenequinonoid.
 87. The composition of claim 84, wherein saidphotosensitizing agent is an agent shown in any of FIGS. 1-12. 88.-90.(canceled)
 91. A method of inhibiting the growth or proliferation of amicroorganism or a biofilm, said method comprising contacting saidmicroorganism or biofilm with a composition of claim
 84. 92. The methodof claim 91, further comprising exposing said microorganism or biofilmto a light source.
 93. The method of claim 91, wherein saidmicroorganism is a microorganism selected from the group consisting of abacterium, a yeast, a fungus, a protozoan, and a virus.
 94. The methodof claim 91, wherein said biofilm comprises a bacterial film.
 95. Themethod of claim 91, wherein said biofilm is a biofilm on an implanted orimplantable medical device.
 96. The method of claim 91, wherein saidmicroorganism or biofilm is an organism or biofilm in an oral cavity.97. A formulation comprising: a targeting peptide, an antimicrobialpeptide, and/or a STAMP; and a salt at a concentration comparable tothat found in phosphate buffered saline (PBS) ranging from about 0.5×PBSto about 2.5×PBS.
 98. The formulation of claim 97, wherein saidformulation comprises a targeting peptide found in Tables 3 or 10.99-103. (canceled)
 104. The formulation of claim 97, wherein saidformulation comprises the amino acid sequence of the C₁₆G2 STAMP(TFFRLFNRSFTQALGKGGGKNLRIIRKGIHIIKKY (SEQ ID NO:2). 105-112. (canceled)